Licorice (Glycyrrhiza glabra), a medicinal plant belonging to the Fabaceae family, has been used in traditional medicine for centuries to manage various health conditions. Glycyrrhizin (GLY), one of its principal bioactive constituents, has attracted scientific interest because of its antibacterial, antiviral, anti-inflammatory, immunomodulatory and hepatoprotective properties. Although its antiviral effects have been extensively investigated, its antibacterial mechanisms and potential applications against drug-resistant pathogens are receiving increasing attention. Antibacterial activity has been associated with the inhibition of bacterial enzymes, disruption of membrane function and modulation of host immune responses. However, much of the mechanistic evidence remains preclinical, and further clinical research is required to establish its therapeutic utility.
Antibacterial properties and mechanisms of action
GLY has demonstrated antibacterial effects through several mechanisms, including interference with bacterial enzymes, alteration of cell membrane formation and permeability, and enhancement of antimicrobial activity when combined with selected antibiotics. Its effects may also be mediated through host immune pathways that support pathogen clearance.
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Target organism or application |
Proposed mechanism or effect |
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Helicobacter pylori |
Inhibition of bacterial enzyme activity and modulation of HMGB1-associated pathways, potentially improving lysosomal activity and limiting intracellular bacterial growth. |
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Klebsiella pneumoniae |
Inhibition of N-acetyltransferase (NAT) activity has been associated with antibacterial effects. |
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Salmonella enterica |
Interference with glycosyltransferase (GTase)-associated processes may affect bacterial adhesion and biofilm formation. |
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Pseudomonas aeruginosa |
Modulation of HMGB1-related inflammatory signalling may reduce tissue inflammation while supporting antimicrobial peptide production. |
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Staphylococcus aureus |
Inhibition of p38 signalling may reduce inflammatory mediator production; GLY-based hydrogels have also shown potential in infected wound models. |
GLY may also affect bacterial membrane permeability and drug-efflux activity, potentially increasing bacterial susceptibility to antimicrobial agents. Its combination with Gentamicin has demonstrated synergistic effects against Gentamicin-resistant Enterobacteriaceae in experimental research. Furthermore, its amphiphilic properties may facilitate the formation of supramolecular complexes with hydrophobic drugs, improving their solubility and potentially influencing drug delivery. These findings support further investigation into GLY as an adjunct to antimicrobial treatment, rather than as a replacement for established antibiotics.
Anti-inflammatory and immunomodulatory effects
Beyond its direct antibacterial activity, GLY may contribute to infection control by regulating host inflammatory responses. Its interaction with high-mobility group box 1 (HMGB1), a damage-associated molecular pattern protein, has been investigated as a mechanism for limiting excessive inflammation. By modulating HMGB1-associated signalling and downstream pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), the production of pro-inflammatory cytokines may be reduced.
In experimental models of P. aeruginosa infection, GLY-mediated modulation of inflammatory signalling has been associated with reduced inflammatory cell recruitment and enhanced antimicrobial peptide production. In burn-wound models, changes in inflammatory mediator expression and increased β-defensin production have also been reported. These findings suggest that antibacterial effects may be complemented by host-directed mechanisms that limit infection-associated tissue damage. Nevertheless, the balance between pathogen clearance and immune suppression requires further investigation.
Other therapeutic applications
GLY has been investigated for several pharmacological properties beyond antibacterial activity.
- Hepatoprotective effects: Injectable GLY preparations have been used for chronic hepatitis, with clinical studies reporting reductions in alanine aminotransferase levels. However, efficacy depends on the specific indication and formulation, and these findings should not be generalised to all liver diseases.
- Antiviral activity: Inhibitory effects against several viruses have been investigated experimentally, contributing to GLY’s established prominence in antiviral research.
- Metabolic effects: Potential benefits in type 2 diabetes mellitus have been explored, including effects on glucose regulation, insulin resistance and lipid metabolism. Clinical efficacy remains insufficiently established.
- Anti-inflammatory applications: Effects involving HMGB1-associated signalling have been investigated in allergic asthma and experimental spinal cord injury, suggesting broader potential in inflammatory conditions.
These applications remain at different stages of investigation, and evidence from experimental models cannot independently establish clinical effectiveness.
Safety and future perspectives
The potential use of GLY in antibacterial therapy is particularly relevant amid increasing antimicrobial resistance. Its ability to influence bacterial survival, membrane permeability, biofilm-associated processes and antibiotic activity warrants further investigation. GLY-containing hydrogels have also shown promise in experimental wound healing, including wounds infected with S. aureus, through effects on bacterial burden, granulation tissue formation, collagen deposition and inflammation.
However, natural origin does not guarantee safety. Prolonged or excessive exposure to GLY can cause adverse effects, including sodium and fluid retention, hypertension, and hypokalaemia. Potential drug interactions and differences between oral, topical and injectable formulations must therefore be considered. Further research should establish appropriate dosing, safety profiles, pharmacokinetics and efficacy in controlled clinical trials, particularly for antibacterial indications.
Conclusion
GLY is a promising licorice-derived compound with potential antibacterial, immunomodulatory, anti-inflammatory and hepatoprotective properties. Its proposed antibacterial mechanisms include interference with bacterial enzymes and membrane function, modulation of host immune responses, and enhancement of selected antibiotics. Although experimental findings support further investigation, its effectiveness against clinically significant infections and multidrug-resistant pathogens remains to be established. Rigorous clinical studies are needed to clarify its therapeutic role, safety and potential value as an adjunct to conventional antimicrobial treatment.1,2
References:
- Chen RY, Shi JJ, Liu YJ, et al. The State-of-the-Art Antibacterial Activities of Glycyrrhizin: A Comprehensive Review. Microorganisms. 2024;12(6):1155. Published 2024 Jun 6. doi:10.3390/microorganisms12061155 https://pmc.ncbi.nlm.nih.gov/articles/PMC11206003/#sec5-microorganisms-12-01155
- Bisht D, Rashid M, Arya RKK, et al. Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: Potential pharmacological applications with mechanistic insight. Phytomed Plus. 2022;2(1):100206. doi:10.1016/j.phyplu.2021.100206 https://pmc.ncbi.nlm.nih.gov/articles/PMC8683220/