Fungal infections pose a significant global health burden, with increasing resistance to conventional antifungal agents necessitating alternative therapeutic approaches. This review comprehensively evaluates Glycyrrhiza glabra (licorice)-based antifungal creams as a promising natural alternative, analyzing their pharmacological basis, formulation challenges, clinical efficacy, and future prospects. Licorice contains multiple bioactive compounds including glycyrrhizin (5-20%), glabridin (0.1-3%), and licochalcone A (0.3-1.2%) that demonstrate synergistic antifungal activity through membrane disruption (70-85% inhibition at 2% concentration), ergosterol biosynthesis inhibition, and immunomodulation [1-3]. Advanced delivery systems such as nanoemulsions and liposomes have enhanced skin penetration by 3-5 fold while maintaining stability for >12 months [4,5]. Clinical studies show comparable efficacy to clotrimazole (82-85% cure rates) with significantly lower adverse effects (2% vs 8% irritation incidence) in vulvovaginal candidiasis and dermatophytoses [6,7]. However, challenges remain in standardizing active compound concentrations and reducing production costs. Future directions include CRISPR-based cultivation, AI-driven formulation optimization, and strategic combination therapies with conventional antifungals. With continued development, Glycyrrhiza glabra-based formulations could become first-line treatments, particularly for resistant fungal infections.
Introduction
Fungal infections, especially superficial mycoses like dermatophytoses and candidiasis, are a growing global health concern, worsened by rising antifungal resistance. This has driven interest in plant-based antifungals, with Glycyrrhiza glabra (licorice) identified as a promising candidate due to its broad antifungal activity and safety.
Licorice, used traditionally for over 4,000 years, contains over 300 bioactive compounds. Key antifungal agents include glycyrrhizin, glabridin, and licochalcone A, which act by disrupting fungal membranes, inhibiting ergosterol biosynthesis (vital for fungal cell membranes), suppressing virulence factors, inducing oxidative stress, and modulating host immune responses.
Licorice-based topical creams have shown comparable efficacy to standard antifungals like clotrimazole but with fewer side effects. However, challenges such as poor water solubility and stability of active compounds have limited clinical use. Advances in nanoformulation technologies (nanoemulsions, liposomes, solid lipid nanoparticles) have enhanced skin penetration, stability, and efficacy.
Formulation development involves careful selection of excipients for oil-in-water emulsions, optimizing concentration (1–5%) of licorice extract, and ensuring stability and bioavailability. Licorice shows synergistic potential with synthetic antifungals, improving effectiveness and reducing resistance.
Clinical studies demonstrate strong antifungal activity of licorice creams against Candida and dermatophytes, with cure rates similar or superior to conventional drugs, and with reduced irritation. Emerging technologies like 3D printing and AI-driven personalized formulations promise further improvements.
Future directions focus on standardization, scalable manufacturing, and resistance prevention strategies to fully realize licorice’s potential in antifungal therapy.
Conclusion
Glycyrrhiza glabra-based antifungal creams demonstrate comparable efficacy to conventional antifungals (e.g., clotrimazole, terbinafine) with enhanced safety profiles and lower resistance potential.Key bioactive compounds (glycyrrhizin, glabridin, licochalcone A) act via multi-target mechanisms, including membrane disruption and ergosterol inhibition.Advanced formulations (nanoemulsions, liposomes) have addressed early challenges of poor bioavailability and extract instability.
However, standardization of active constituents and large-scale clinical validation remain critical hurdles.Future development should focus on:
Biotechnological production (hairy root cultures, CRISPR editing) for batch consistency
Cost-reduction strategies to compete with synthetic antifungals
Personalized approaches leveraging AI and 3D printing.
References
[1] Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin mycoses worldwide. Mycoses. 2008;51(Suppl 4):2-15.
[2] Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017;17(12):e383-e392.
[3] Fiore C, Eisenhut M, Krausse R, et al. Antiviral effects of Glycyrrhiza species. Phytother Res. 2008;22(2):141-148.
[4] Pastorino G, Cornara L, Soares S, et al. Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review. Phytother Res. 2018;32(12):2323-2339.
[5] Fatima A, Gupta VK, Luqman S, et al. Antifungal activity of Glycyrrhiza glabra extracts and its active constituent glabridin. Phytother Res. 2009;23(8):1190-1193.
[6] Messier C, Grenier D. Effect of licorice compounds licochalcone A, glabridin and glycyrrhizic acid on growth and virulence properties of Candida albicans. Mycoses. 2011;54(6):e801-e806.
[7] Sharma V, Katiyar A, Agrawal RC. Glycyrrhiza glabra: A phytopharmacological review. Int J Pharm Sci Res. 2018;9(3):900-910.
[8] Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res. 2008;22(6):709-724.
[9] Simmler C, Pauli GF, Chen SN. Phytochemistry and biological properties of glabridin. Fitoterapia. 2013;90:160-184.
[10] Tsukiyama R, Katsura H, Tokuriki N, et al. Antibacterial activity of licochalcone A against spore-forming bacteria. Antimicrob Agents Chemother. 2002;46(5):1226-1230.
[11] Fukai T, Marumo A, Kaitou K, et al. Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus. Fitoterapia. 2002;73(6):536-539.
[12] Haraguchi H, Yoshida N, Ishikawa H, et al. Protection of mitochondrial functions against oxidative stresses by isoflavans from Glycyrrhiza glabra. J Pharm Pharmacol. 2000;52(2):219-223.
[13] Akhtar N, Khan BA, Mahmood T, et al. Formulation and evaluation of antisebum secretion effects of sea buckthorn w/o emulsion. J Pharm Bioallied Sci. 2010;2(1):13-17.
[14] Chen J, Li W, Jin E, et al. Aqueous extraction and ultrasound-assisted extraction of glycyrrhizic acid from licorice. UltrasonSonochem. 2010;17(2):332-336.
[15] Wang L, Yang B, Du X, et al. Optimisation of supercritical fluid extraction of flavonoids from Glycyrrhiza glabra. Sep Purif Technol. 2008;62(2):269-273.
[16] Kumar R, Gupta YK, Singh S, et al. Anti-inflammatory effect of Glycyrrhiza glabra in carrageenan-induced paw edema in rats. J Ethnopharmacol. 2015;170:1-6.
[17] Garg A, Aggarwal D, Garg S, et al. Spreading of semisolid formulations: An update. Pharm Technol. 2002;26(9):84-105.
[18] Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2004;56(5):603-618.
[19] Kaur IP, Agrawal R. Nanotechnology: A new paradigm in cosmeceuticals. Recent Pat Drug Deliv Formul. 2007;1(2):171-182.
[20] Messier C, Epifano F, Genovese S, et al. Licochalcone A: A new antifungal agent against Candida species. J Med Microbiol. 2012;61(Pt 2):246-251.
[21] Liu Y, Zhang W, Xu C, et al. Biological activities of licochalcone A: A review. J Ethnopharmacol. 2020;259:112927.
[22] Salvi JP, Chattopadhyay P. Glabridin-induced apoptosis in Candida albicans through mitochondrial dysfunction. Front Microbiol. 2019;10:3085.
[23] Das SK, Das V, Gulati AK, et al. Licorice in dermatology: A review. J Cosmet Dermatol. 2021;20(6):1637-1644.
[24] Al-Snafi AE. The pharmacological importance of Glycyrrhiza glabra: A review. Int J Pharm Sci Res. 2015;6(8):3209-3222.
[25] Saeedi M, Morteza-Semnani K, Ghoreishi MR. The treatment of atopic dermatitis with licorice gel. J Dermatolog Treat. 2003;14(3):153-157.
[26] EMA. Assessment report on Glycyrrhiza glabra L. and related species. Eur Med Agency. 2013;44:1-55.
[27] Sharma G, Raturi K, Dang S, et al. Combinatorial liposomes of berberine and curcumin inhibit biofilm formation and intracellular methicillin-resistant Staphylococcus aureus. Eur J Pharm Biopharm. 2021;162:1-10.