Compendium of the most significant studies with reference to properties, intake, effects.

Rani K, Devi N, Saharan V, Kharb P. Glycyrrhiza glabra: An Insight to Nanomedicine. J Nanosci Nanotechnol. 2021 Jun 1;21(6):3367-3378. doi: 10.1166/jnn.2021.19007.

Abstract Glycyrrhiza glabra Linn (Fabaceae), commonly known as Licorice/Liquorice, Mulahatti; is an undershrub. The dried, peeled or unpeeled underground stems and roots are used for the treatment of upper respiratory tract ailments, immunodeficiency, endocrine disorders, skin, liver, joint and heart diseases. Medicinal properties of this plant are enormous and offer it as one of the greatest candidates in the field of Nanomedicine. The Nanomedicine has dedicated to safeguard and upgrade human health using the nanotechnology. Bioactive constituents of this plant perform versatile pharmacological actions and can be used as good Bioanalytical tools. Therefore, an updated overview on current knowledge of green synthesis of nanoparticles (NPs), nanoformulations and surface modification using G. glabra is provided here in order to explore its therapeutic potential especially antifungal and antibacterial activities. In our lab, we have synthesized silver nanoparticles (Ag NPs) using leaves and rhizome parts of G. glabra.

Simons R, Vincken JP, Mol LA, The SA, Bovee TF, Luijendijk TJ, Verbruggen MA, Gruppen H. Agonistic and antagonistic estrogens in licorice root (Glycyrrhiza glabra). Anal Bioanal Chem. 2011 Jul;401(1):305-13. doi: 10.1007/s00216-011-5061-9. 

Abstract. The roots of licorice (Glycyrrhiza glabra) are a rich source of flavonoids, in particular, prenylated flavonoids, such as the isoflavan glabridin and the isoflavene glabrene. Fractionation of an ethyl acetate extract from licorice root by centrifugal partitioning chromatography yielded 51 fractions, which were characterized by liquid chromatography-mass spectrometry and screened for activity in yeast estrogen bioassays. One third of the fractions displayed estrogenic activity towards either one or both estrogen receptors (ERs; ERα and ERβ). Glabrene-rich fractions displayed an estrogenic response, predominantly to the ERα. Surprisingly, glabridin did not exert agonistic activity to both ER subtypes. Several fractions displayed higher responses than the maximum response obtained with the reference compound, the natural hormone 17β-estradiol (E(2)). The estrogenic activities of all fractions, including this so-called superinduction, were clearly ER-mediated, as the estrogenic response was inhibited by 20-60% by known ER antagonists, and no activity was found in yeast cells that did not express the ERα or ERβ subtype. Prolonged exposure of the yeast to the estrogenic fractions that showed superinduction did, contrary to E(2), not result in a decrease of the fluorescent response. Therefore, the superinduction was most likely the result of stabilization of the ER, yeast-enhanced green fluorescent protein, or a combination of both. Most fractions displaying superinduction were rich in flavonoids with single prenylation. Glabridin displayed ERα-selective antagonism, similar to the ERα-selective antagonist RU 58668. Whereas glabridin was able to reduce the estrogenic response of E(2) by approximately 80% at 6 × 10(-6) M, glabrene-rich fractions only exhibited agonistic responses, preferentially on ERα.

Gioti K, Papachristodoulou A, Benaki D, Beloukas A, Vontzalidou A, Aligiannis N, Skaltsounis AL, Mikros E, Tenta R. Glycyrrhiza glabra-Enhanced Extract and Adriamycin Antiproliferative Effect on PC-3 Prostate Cancer Cells. Nutr Cancer. 2020;72(2):320-332. doi: 10.1080/01635581.2019.1632357.

Abstract Prostate cancer is the second most commonly diagnosed cancer in men worldwide, which is almost incurable, once it progresses into the metastatic stage. Adriamycin (ADR) is a known chemotherapeutic agent that causes severe side effects. In recent years, studies in natural plant products have revealed their anticancer activities. In particular, Glycyrrhiza glabra enhanced extract (GGE), commonly known as licorice, has been reported to exert antiproliferative properties against cancer cells. In this study, the cytotoxic potential of GGE was assessed in PC-3 cells, when it is administrated alone or in combination with Adriamycin. PC-3 cells were treated with GGE and/or ADR, and the inhibition of cell proliferation was evaluated by the MTT assay. Cell cycle alterations and apoptosis rate were measured through flow cytometry. Expression levels of autophagy-related genes were evaluated with specific ELISA kits, Western blotting, and real-time PCR, while NMR spectrometry was used to identify the implication of specific metabolites. Our results demonstrated that GGE alone or in co-treatment with ADR shows antiproliferative properties against PC-3 cells, which are mediated by both apoptosis and autophagy mechanisms.

Li W, Asada Y, Yoshikawa T. Antimicrobial flavonoids from Glycyrrhiza glabra hairy root cultures. Planta Med. 1998 Dec;64(8):746-7. doi: 10.1055/s-2006-957571. 

Abstract.  A new compound named licoagrodione was isolated from the hairy root cultures of Glycyrrhiza glabra (Fabaceae) together with five known prenylated flavonoids. The structure of licoagrodione has been elucidated on the basis of spectral evidence and it was found to have antimicrobial activity indicated by disc diffusion method.

Yavuz Kocaman A, Güzelkokar M. The genotoxic and antigenotoxic potential of the methanolic root extract of Glycyrrhiza glabra L. on human peripheral blood lymphocytes. Drug Chem Toxicol. 2018 Jul;41(3):368-375. doi: 10.1080/01480545.2018.1435686.

Abstract Glycyrrhiza glabra L. (licorice) is one of the most important medicinal plants, which is widely used throughout the world both in traditional and contemporary medical industries. This study was undertaken to investigate the potential genotoxic activity of G. glabra methanolic root extract, and its possible antigenotoxic properties against mitomycin C (MMC)-induced DNA damage in in vitro chromosome aberrations (CAs) and cytokinesis-block micronucleus (CBMN) assays in human peripheral blood lymphocytes (PBLs). Lymphocytes were treated with 25, 50, and 100 µg/ml G. glabra methanolic root extract alone as well as in combination with MMC (0.1 µg/ml) for 24 and 48 h treatment periods. It was found that there were no statistically significant differences between the negative control and the groups treated with all concentrations of G. glabra root extract of alone (p > 0.05), demonstrating the absence of genotoxic effects at both 24 and 48 h treatment periods. Besides, the co-treatment of G. glabra methanolic root extract and MMC significantly decreased the percentage of structural CAs and MN formation when compared with the culture treated with MMC alone (p < 0.001). In addition, the negative interaction factor (IF) values obtained for all combinations represent an antagonistic effect of G. glabra versus MMC. We can state that this extract acts as an antagonist and markedly decreased MMC-induced cytogenotoxicity. In conclusion, the present results demonstrate that in the tested experimental conditions, G. glabra methanolic root extract is not genotoxic in cultured human PBLs and has also antigenotoxic activity against MMC, which is widely used in chemotherapy against cancer.

Malvania EA, Sharma AS, Sheth SA, Rathod S, Chovatia NR, Kachwala MS. In Vitro Analysis of Licorice (Glycyrrhiza glabra) Root Extract Activity on Streptococcus mutans in Comparison to Chlorhexidine and Fluoride Mouthwash. J Contemp Dent Pract. 2019 Dec 1;20(12):1389-1394. 

Abstract Aim: The present study was done to determine the activity of licorice root extract on Streptococcus mutans (S. mutans) in comparison to chlorhexidine and fluoride mouthwash. Materials and methods: In the current study, the different concentrations of aqueous and ethanolic licorice root extract were subjected to microbiological assay and zone of inhibition was determined against S. mutans by agar ditch method. Minimum inhibitory concentration (MIC) of aqueous and ethanolic solution was obtained by using broth dilution method and agar dilution method. Chlorhexidine and fluoride mouthwash were kept as a positive control in the present study. One-way ANOVA along with Tukey post hoc test were used at 5% level of significance to analyze data. Results: Mean zone of inhibition of chlorhexidine mouthwash, fluoride mouthwash, aqueous and ethanolic licorice root extracts against S. mutans at 24 hours were 23 mm, 14.2 mm, 15.8 mm and 22.4 mm, respectively. Minimum inhibitory concentration of aqueous and ethanolic licorice root extract on S. mutans was 20 mg/mL and 12.5 mg/mL, respectively by both broth dilution method and agar dilution method. Conclusion: The antibacterial effect produced by ethanolic licorice root extract on S. mutans was comparable to chlorhexidine mouthwash while significantly higher in comparison with aqueous form and fluoride mouthwash. Clinical significance: The interest in the plants with antibacterial and anti-inflammatory activity has increased now days to treat various dental diseases as consequences of current problems associated with the conventional agents. Licorice root is easily available, economically feasible and culturally acceptable and may possess minimal side effects as compared to conventional means of chemicotherapeutic agents used for reduction of S. mutans in oral cavity and hence can be recommended for prevention of dental caries.

Komes D, Belščak-Cvitanović A, Jurić S, Bušić A, Vojvodić A, Durgo K. Consumer acceptability of liquorice root (Glycyrrhiza glabra L.) as an alternative sweetener and correlation with its bioactive content and biological activity. Int J Food Sci Nutr. 2016;67(1):53-66. doi: 10.3109/09637486.2015.1126563.

Abstract. Consumer acceptability and sensory properties of liquorice root (Glycyrrhiza glabra L.) were evaluated. Quantitation of total polyphenolics and glycyrrhizic acid (GA), as well as the antioxidant capacity of liquorice extracts, was conducted and their biological effects (cytotoxic, antioxidative/pro-oxidative activity, lipid peroxidation on human laryngeal carcinoma cell line) compared to the ones of their predominant bioactive compound - GA. Conducted consumer survey revealed poor familiarity with liquorice (12.37% of correspondents), but willingness towards its use as an alternative sweetener (77.32% of consumers). Polyphenolic content of evaluated extracts ranged from 1018.18 to 1277.27 mg gallic acid equivalents (GAE)/l while GA content varied between 2179.53 and 2944.13 mg/l. The most pronounced cytotoxic effect (60%) and lipid peroxidation were exerted by treatment with the highest applied extract concentrations (10 mg/ml). Pure GA exhibited cytotoxic and pro-oxidative effects at concentrations of 0.12-0.6 mg/ml. Due to high GA content, coupled with its pronounced cytotoxic activity, the intake of liquorice root should be limited.

Schmid C, Mittermeier-Kleßinger V, Tabea Peters VC, Berger F, Kramler M, Heuberger H, Rinder R, Hofmann T, Gutjahr C, Dawid C. Quantitative Mapping of Flavor and Pharmacologically Active Compounds in European Licorice Roots (Glycyrrhiza glabra L.) in Response to Growth Conditions and Arbuscular Mycorrhiza Symbiosis. J Agric Food Chem. 2021 Nov 10;69(44):13173-13189. doi: 10.1021/acs.jafc.1c05576.

Abstract. Application of a sensitive UHPLC-MS/MSMRM method enabled the simultaneous quantitation of 23 sweet-, licorice-, and bitter-tasting saponins in Glycyrrhiza glabra L., Glycyrrhiza uralensis Fisch., different licorice plants and root compartments, processed licorice, as well as different Glycyrrhiza spp. The combination of quantitative data with sweet, licorice, and bitter taste thresholds led to the determination of dose-over-threshold factors to elucidate the sweet, licorice, and bitter impact of the individual saponins with and without mycorrhiza symbiosis to evaluate the licorice root quality. Aside from glycyrrhizin (1), which is the predominant sweet- and licorice-tasting saponin in all licorice samples, 20 out of 22 quantitated saponins contributed to the taste profile of licorice roots. Next to sweet-/licorice-tasting glycyrrhizin (1), 24-hydroxy-glycyrrhizin (9), 30-hydroxy-glycyrrhizin (11), and 11-deoxo-24-hydroxy-glycyrrhizin (14) as well as licorice tasting saponins 20α-galacturonic acid glycyrrhizin (17), 24-hydroxy-20α-glycyrrhizin (21), and 11-deoxo-glycyrrhizin (12) were determined as key contributors to licorice root's unique taste profile. A quantitative comparison of 23 saponins as well as 28 polyphenols between licorice roots inoculated with arbuscular mycorrhiza fungi and controls showed that important taste-mediating saponins were increased in mycorrhizal roots, and these alterations depended on the growth substrate and the level of phosphate fertilization.

Visavadiya NP, Soni B, Dalwadi N. Evaluation of antioxidant and anti-atherogenic properties of Glycyrrhiza glabra root using in vitro models. Int J Food Sci Nutr. 2009;60 Suppl 2:135-49. doi: 10.1080/09637480902877998. 

Abstract. The aim of present study was to evaluate antioxidant property of Glycyrrhiza glabra root extracts using in vitro models. The dose-dependent aqueous and ethanolic extracts demonstrated the scavenging activity against nitric oxide (concentration that caused 50% inhibition of nitric oxide radicals [IC(50)]=72 and 62.1 microg/ml, respectively), superoxide (IC(50)=64.2 and 38.4 microg/ml, respectively), hydroxyl (IC(50)=81.9 and 63 microg/ml, respectively), DPPH (IC(50)=43.6 and 28.3 microg/ml, respectively) and ABTS(*+) (IC(50)=77.3 and 57.2 microg/ml, respectively) radicals. Further, both extracts showed strong reducing power and iron-chelating capacities. In the Fe(2+)/ascorbate system, both extracts were found to inhibit mitochondrial fraction lipid peroxidation. In copper-catalyzed human serum and low-density lipoprotein oxidation models, both extracts significantly (P<0.05) lengthened the lag phase along with a decline in the oxidation rate, conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substance formation. In conclusion, ethanolic extract of G. glabra possess considerable antioxidant activity and protective effect against the human lipoprotein oxidative system.