Hepatoprotective Potential of Glycyrrhizin: A Critical Evaluation of Antioxidant, Anti-Inflammatory and Anti-fibrotic Evidence
Manoj Todkar *
Rashtriya College of Pharmacy, Hatnoot, Kannad, Maharashtra-431103, India.
Suresh Waghamare
Rashtriya College of Pharmacy, Hatnoot, Kannad, Maharashtra-431103, India.
*Author to whom correspondence should be addressed.
Abstract
Glycyrrhizin, a triterpenoid saponin obtained principally from liquorice species such as Glycyrrhiza glabra and Glycyrrhiza uralensis, has a long history of pharmacological use in liver disorders, yet the evidential basis for its hepatoprotective reputation is unusually heterogeneous. This critical narrative review evaluates glycyrrhizin, its principal metabolite glycyrrhetinic acid, and clinically used glycyrrhizin preparations through three mechanistically connected domains: antioxidant and redox-modulating activity, control of sterile and immune-mediated inflammation, and attenuation of fibrogenesis. Literature published from 1980 to 4 August 2026 was selected from major biomedical and multidisciplinary scholarly sources, supplemented by citation searching and verification of bibliographic metadata and digital object identifiers. Across toxic, ischaemia-reperfusion, immune-mediated, metabolic and cholestatic models, glycyrrhizin repeatedly reduces aminotransferase release, lipid peroxidation and inflammatory signalling, with recurrent involvement of high-mobility group box 1, nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signalling, inflammasome-related pathways and macrophage responses. Anti-fibrotic evidence is biologically plausible but more conditional: glycyrrhetinic acid can suppress transforming growth factor-β/Smad-dependent collagen transcription and, in activated stellate cells, can also induce pro-apoptotic oxidative stress, demonstrating that redox effects are cell-state dependent rather than uniformly antioxidant. Human evidence is strongest for improvement of biochemical liver-injury markers with selected injectable glycyrrhizin derivatives and preparations; evidence for durable histological benefit, prevention of cirrhosis, hepatocellular carcinoma, transplantation or mortality remains substantially weaker. Interpretation is further complicated by oral conversion of glycyrrhizin to glycyrrhetinic acid, formulation-specific pharmacology, high preventive doses in animal studies and pseudoaldosteronism mediated by glycyrrhetinic-acid metabolites. Glycyrrhizin therefore represents a mechanistically credible hepatoprotective scaffold, but clinical translation requires formulation-specific exposure data, modern comparator-controlled trials and outcomes that extend beyond aminotransferase normalisation.
Keywords: Glycyrrhizic acid, glycyrrhetinic acid, high-mobility group box 1, oxidative stress, hepatic stellate cells, liver fibrosis, drug-induced liver injury