Glycyrrhizin (Triterpene Saponin · Hepatoprotective · Antiviral · HMGB1 Inhibitor)

Compound	Glycyrrhizin (Glycyrrhizic Acid)
Chemical class	Terpenoid — Triterpene Saponin (Oleanane skeleton + disaccharide)
CAS	1405-86-3
Primary source	Glycyrrhiza glabra, G. uralensis (licorice root)
Key applications	Hepatoprotective, antiviral, anti-inflammatory, sweet taste modifier
Claim strength	Moderate
Typical form	Licorice root extract; glycyrrhizin isolate; DGL (deglycyrrhizinated) licorice
Buy from Herbuno	Licorice Root Extract Powder | Mulethi → DGL Licorice Extract Powder | Mulethi →

Name origin: From Greek glykys (sweet) + rhiza (root) — licorice root, the primary source. Glycyrrhizin (glycyrrhizic acid) is a triterpene saponin — the aglycone glycyrrhetinic acid linked to a disaccharide (glucuronyl glucuronide). It is approximately 50–150× sweeter than sucrose and is responsible for licorice’s characteristic sweet taste. Traditional use: Licorice root (Gan Cao in TCM; Yashtimadhu in Ayurveda) is one of the most widely used medicinal plants globally — used for gastric ulcers, respiratory complaints, adrenal support, hormonal balance, and as a harmonising agent in compound TCM prescriptions. Glycyrrhizin is identified as a key bioactive, though some applications are associated more with other licorice constituents (flavanones, chalcones) in DGL form. Research trajectory: Glycyrrhizin has a long pharmaceutical history — intravenous glycyrrhizin preparations (Stronger Neo-Minophagen C, SNMC) are approved in Japan for chronic hepatitis B and C treatment. Strong antiviral activity (SARS, SARS-CoV-2, HIV, influenza) has driven renewed research interest. The pseudoaldosteronism safety concern limits high-dose oral use. Commercial source: Licorice Root Extract Powder and DGL Licorice Extract Powder from Herbuno. See sourcing options below.

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Evidence for Glycyrrhizin Applications

Hepatoprotective — chronic viral hepatitis: Intravenous glycyrrhizin (SNMC, 40–240 mg/day IV) is an approved pharmaceutical in Japan for normalising liver enzymes in chronic hepatitis B and C. Multiple Japanese RCTs confirm efficacy for ALT/AST normalisation and prevention of hepatocellular carcinoma in long-term hepatitis C patients. Oral glycyrrhizin has less clear clinical evidence due to bioavailability differences. Claim strength: Moderate (IV pharmaceutical data; oral supplement translation limited).

Antiviral — broad-spectrum: Glycyrrhizin inhibits viral replication in vitro against SARS-CoV, SARS-CoV-2 (protease and spike protein binding), HIV (post-adsorption entry inhibition), influenza A, RSV, and herpes simplex virus. The antiviral mechanism involves direct virus-cell membrane interaction and interferon induction. Claim strength: Moderate (in vitro and animal; limited human antiviral supplement data).

Anti-inflammatory — HMGB1 inhibition: Glycyrrhizin is a direct inhibitor of HMGB1 (high mobility group box 1 protein) — a late mediator of systemic inflammation and sepsis. This mechanism is distinct from most botanical anti-inflammatories targeting NF-κB or COX enzymes and is relevant to severe inflammatory conditions. Claim strength: Moderate.

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Dosage & Formulator Specification

CRITICAL SAFETY NOTE: Chronic oral glycyrrhizin intake above 100 mg/day causes pseudoaldosteronism — inhibition of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) allows cortisol to activate mineralocorticoid receptors, causing sodium retention, potassium loss, hypertension, and oedema. This is a real, dose-dependent, and potentially serious adverse effect. WHO recommends maximum 100 mg/day glycyrrhizin for chronic consumption. The EU has established a tolerable daily intake (TDI) guidance.

For oral supplement formulations targeting licorice bioactives without pseudoaldosteronism risk: use DGL (deglycyrrhizinated licorice) — glycyrrhizin removed to <3% — which retains flavanones (liquiritin, isoliquiritigenin) and other non-glycyrrhizin actives. For formulations specifically requiring glycyrrhizin activity (antiviral, hepatoprotective): keep below 100 mg/day glycyrrhizin equivalent, declare glycyrrhizin content on label, and include advisory language for hypertension, cardiovascular, and kidney disease patients.

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Frequently Asked Questions — Glycyrrhizin

What is pseudoaldosteronism and why is it a safety concern with licorice?
Cortisol and aldosterone (the mineralocorticoid) both bind the mineralocorticoid receptor. Normally, 11β-HSD2 enzyme in the kidney rapidly converts cortisol to cortisone (inactive), preventing cortisol from activating aldosterone receptors. Glycyrrhizin (and its aglycone glycyrrhetinic acid) inhibits 11β-HSD2, allowing cortisol to accumulate and act on mineralocorticoid receptors — producing aldosterone-like effects: sodium retention, potassium loss, hypertension, and oedema. This is the mechanism underlying the well-documented cases of licorice-induced hypertension and hypokalaemia.

Does DGL licorice retain the same therapeutic activity as standard licorice extract?
No — DGL retains flavanone and flavonoid activity (liquiritin, isoliquiritigenin, glabridin) but loses the antiviral, hepatoprotective (HMGB1 inhibition), and sweet-taste modifying properties of glycyrrhizin. DGL is appropriate for GI applications (ulcer healing, reflux — where flavanones and mucus-stimulating properties are the therapeutic basis) and for long-term oral use where pseudoaldosteronism risk must be avoided. Standard licorice extract is required for antiviral and HMGB1-inhibiting applications.

Can glycyrrhizin be used as a natural sweetener?
Yes — glycyrrhizin is used as a natural sweetening agent (E958 in the EU). At flavouring concentrations (below 100 mg/day from food and supplement use combined), it contributes to product sweetness while staying within safe limits. Licorice-flavoured confectionery, herbal supplements, and functional foods frequently use licorice extract (glycyrrhizin) for its sweet-bitter taste profile. Note that EU regulations require labelling warnings on confectionery products with significant glycyrrhizin content.

Is glycyrrhizin active against SARS-CoV-2?
In vitro studies demonstrate glycyrrhizin inhibits SARS-CoV-2 main protease (3CL-Pro) and spike protein-ACE2 interaction at low micromolar concentrations. These findings generated significant research interest during the COVID-19 pandemic. Inhalation delivery of glycyrrhizin has been proposed for direct respiratory tract antiviral activity. Human clinical evidence for COVID-19 specifically is limited. Glycyrrhizin should not be positioned as a COVID-19 therapeutic, but can be referenced in broad-spectrum antiviral immune support contexts.

Related compounds: Ursolic Acid, Oleanolic Acid, Andrographolide, Ginsenosides

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Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.

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