Table 2.
Summary of the key studies conducted with liquorice‐derived compounds or extract
| Property | Compound | Concentration | Method | Major findings | Reference |
|---|---|---|---|---|---|
| Neuroprotective activity | Glabridin | 5–50 mg/kg | In vivo—oral administration to mice | Improvement of learning and memory in nondiabetic rats; it reversed learning and memory deficits of diabetic rats. Low‐dose glabridin did not alter cognitive function | (Hasanein, 2011) |
| Glycyrrhiza glabra extract | 75–300 mg/kg, 7 days | In vivo—oral administration to Swiss young male albino mice | Production of antidepressant‐like effect in mice in forced swim test and tail suspension test, probably by interaction with adrenergic and dopaminergic system | (Dhingra & Sharma, 2006) | |
| G. glabra aqueous extract | 75–300 mg/kg, 7 days | In vivo—oral administration to mice | Dose of 150 mg/kg significantly improved learning and memory of mice | (Parle, Dhingra, & Kulkarni, 2004) | |
| Sedative activity | Glabridin | 10−12–10−8 M | In vivo—acutely isolated dorsal raphe neurons of a rat | Sedative and hypnotic effects by potentiating GABAergic inhibition in dorsal raphe neurons by GABAA receptor | (Jin et al., 2013) |
| 30 μM | In vitro—Xenopus laevis oocytes expressing recombinant GABAA receptors | Strong potentiating effect on GABAA α1β(1−3)γ2 receptors | (Cho et al., 2010) | ||
| Antidepressive activity | G. glabra aqueous extract | 75–300 mg/kg | In vivo—forced swim test and tail suspension test applied to mice | Antidepressant‐like effect of liquorice extract seems to be mediated by increase of brain norepinephrine and dopamine, but not by increase of serotonin | (Dhingra & Sharma, 2006) |
| Oestrogenic activity | 18β‐Glycyrrhetinic acid | 0–200 μM | In vitro—human breast cancer cells (MCF‐7) | Induction of apoptosis in human breast carcinoma MCF‐7 cells via caspase activation and modulation of Akt/FOXO3a pathway | (Sharma, Kar, Palit, & Das, 2012) |
| Glabridin | 1 nM–10 μM | In vitro—endometrial cell line (Ishikawa cells) | Activation of ER‐α‐SRC‐1‐co‐activator complex, which displays a dose‐dependent increase in oestrogenic activity | (Su Wei Poh, Voon Chen Yong, Viseswaran, & Chia, 2015) | |
| 1 nM–25 μM | In vitro—human breast cancer cells (T‐47D, MCF‐7, and MDA‐MB‐468) | Inhibition of the growth of breast cancer cells | (Su Wei Poh et al., 2015) | ||
| 50 μg, 3–14 days | In vivo—daily feeding of prepubertal female Wistar rats | Stimulation of creatine kinase specific activity | (Tamir, Eizenberg, Somjen, Izrael, & Vaya, 2001) | ||
| Liquorice root extract | 25 μg/day, 2 weeks | In vivo—oral administration to female rats | Increase in creatine kinase activity | (Tamir et al., 2000) | |
| Liquiritigenin | 2–10 μg/ml | In vitro—MCF‐7 and T47D cells | Induction of oestrogen responsive alkaline phosphatase activity in endometrial cancer cells, oestrogen responsive element luciferase in MCF‐7 cells and Tff1 mRNA in T47D cells | (Somjen et al., 2004) | |
| Isoliquiritigenin | 0–0.04 mg/ml | In vivo—intraperitoneal injection of female ICR mice | Improvement of IVF rate | (Tung, Shoyama, Wada, & Tanaka, 2014) | |
| Skin effects | Glycyrrhizinic acid | 20%, 2 weeks | In vivo—double‐blind clinical trial in human patients | Reduction of erythema, oedema, and itching scores | (Halder & Richards, 2004) |
| — | In vitro—topical treatments in human patients during 4 weeks | Lighten hand solar lentigines | (Nerya et al., 2003) | ||
| Glycyrrhetinic acid; glabridin | 0–120 μM | In vitro—human keratinocyte culture | Prevention of oxidative DNA fragmentation and activation of apoptosis‐associated proteins in human keratinocyte | (Grippaudo & Di Russo, 2016) | |
| Glabridin; glabrene; isoliquiritigenin | 0.7 μM (glabridin), 7 μM (glabrene), and 26 μM (isoliquiritigenin) | In vitro—human melanocyte (G361) | Inhibition on tyrosinase‐dependent melanin biosynthesis | (Parvez, Kang, Chung, & Bae, 2007) | |
| Liquorice hydro‐alcoholic extract | 1–2% | In vivo—Wistar albino rats | Potentiation of hair growth activity | (Veratti et al., 2011) | |
| Antiviral activity | Glycyrrhizin | 10 mg/kg (compound) |
In vitro—Vero cells In vivo—ducks |
Stimulation of immune and antiviral effect against DHV | (Soufy et al., 2012) |
| 0.1 μg/ml (extract) | In vitro—human foreskin cell line | Protection of host cells against EV71 infection | (Kuo, Chang, Wang, & Chiang, 2009) | ||
| 316–625 mg/L (compound) | In vitro—Vero cells | Protection against coronavirus | (Cinatl et al., 2003) | ||
| 100 μg/ml (compound) | In vitro—peripheral blood mononuclear cells | Inhibition of nonsyncytium‐inducing variant of HIV replication | (Sasaki, Takei, Kobayashi, Pollard, & Suzuki, 2002) | ||
| 400–1,600 mg/day (compound) | In vitro—human immunodeficiency virus type 1 (HIV‐1) P24 antigen | Inhibition of HIV‐1 replication | (Hattori et al., 1989) | ||
| 80, 160, 240 mg 3× per week or 200 mg 6× per week | In vivo—human patients (intravenous) | Treatment of chronic hepatitis C infection | (van Rossum, Vulto, Hop, & Schalm, 1999) | ||
| 100 mg/day | In vivo—human patients (intravenous) | Prevention of autoimmune hepatitis progression | (Yasui et al., 2011) | ||
| 25–200 μg/ml | In vitro—lung epithelial A549 cells | Reduction of pathogenic H5N1 influenza A virus replication | (Michaelis et al., 2011) | ||
| Anticarcinogenic activity | Glabridin | 0–10 μM, 24, 48, and 72 hr | In vitro—cancer stem cells (CSCs) | Reduction of CSC‐like properties, enhancing the effectiveness of breast cancer therapy | (Jiang et al., 2016) |
| 0–20 mg/kg, 4 weeks | In vivo—BALB/c nude mice | ||||
| 0–100 μM (compound) | In vitro—human hepatic cell lines (Huh7, HepG2, Sk‐Hep‐1) | Induction of apoptosis in Huh7 cells | (Hsieh et al., 2016) | ||
| Licochalcone E | 12.5–50 μM (compound) | In vitro—human oral keratinocytes and human pharyngeal squamous carcinoma cell line | Induction of FaDu cell death | (Yu et al., 2017) | |
| Licochalcone A | 0–500 μM (compound) | In vitro—human gastric cancer cell lines (MKN‐28, AGS, MKN‐45) | Induction of apoptosis of gastric cancer cell via the caspase‐dependent mitochondrial pathway | (Xiao et al., 2011) | |
| Antimicrobial activity | Glabridin | 3.12–25 μg/ml | MIC | Inhibition of the growth of clinical isolates of multidrug‐resistant Staphylococcus aureus | (Fukai et al., 2002a; Singh, Pal, & Darokar, 2015) |
| 3.13–12.5 μg/ml | MIC | ||||
| 29.16 μg/ml | MIC | Decrease of Mycobacterium tuberculosis | (Gupta et al., 2008) | ||
| Glycyrrhetinic acid | 62.5–1.024 mg/L | MIC | Inhibition of the growth of clinical isolates of multidrug‐resistant S. aureus | (Oyama et al., 2016) | |
| 100–400 μg/ml | MIC, MBC | Decrease of Pseudomonas aeruginosa | (Chakotiya, Tanwar, Narula, & Sharma, 2016) | ||
| ≤50 mg/L | MIC | Decrease of Helicobacter pylori | (Krausse, Bielenberg, Blaschek, & Ullmann, 2004) | ||
| Antioxidant activity | Glabridin | 3.12–25 μg/ml | DPPH, FRAP, SOD | Protection of low‐density lipoprotein from oxidation | (Singh et al., 2015) |
| 60 mg | In vivo—oral administration to humans (LDL isolation) | (Carmeli & Fogelman, 2009) | |||
| Licochalcone | 2–20 μg/ml | DPPH, superoxide anion, lipid peroxidation, red blood cells | Inhibition of the microsomal lipid peroxidation | (Haraguchi, Ishikawa, Mizutani, Tamura, & Kinoshita, 1998) | |
| Hepatoprotective activity | Liquorice aqueous extract | 100–300 mg/kg 15 days | In vivo—oral administration to Wistar rats | Stimulation of the antioxidant enzymes and arrest of inflammatory cytokine production | (Huo, Wang, Liang, Bao, & Gu, 2011) |
| G. glabra aqueous root extract | 2 g/day, 2 months | In vivo—humans | ALT and AST decrease | (Hajiaghamohammadi, Ziaee, & Samimi, 2012) | |
| 10, 30, 100 mg/kg |
In vivo—BALB/c mice In vitro—RAW 264.7 macrophages |
Protection against LPS fulminant hepatic failure | (Yin et al., 2017) | ||
| Glycyrrhetinic acid | 0.5–20 μM | Metabolomics | Decrease of inflammation in RAW 264.7 cells | (Liu et al., 2017) | |
| Anti‐inflammatory activity | Glabridin | 75 mg/kg | In vivo—oral administration to mice | Decrease of MIP 1α expression | (Xiao et al., 2010) |
| Glycyrrhizin | 1–100 μM | DPPH, AAPH |
Protection against lipid peroxidation of liposomal membrane Inhibition of ROS |
(Rackova et al., 2007) | |
| 50–200 μg/ml | LPS inflammatory mediators production (TNF‐α, IL‐1β, COX‐2, PG2) | Decrease of endometriosis | (X. R. Wang, et al., 2017) | ||
| 10, 20, 100 mg/kg | In vivo—mice | Decrease of LPS inflammatory mediators | (Yin et al., 2017) |
Note. ALT: alanine aminotransferase; AST: aspartate aminotransferase; DHV: duck hepatitis virus; FRAP: ferric reducing antioxidant potential; ICR: Institute of Cancer Research; IVF: in vitro fertilization; LDL: low‐density lipoprotein; LPS: lipopolysaccharide; MBC: minimum bactericidal concentration; MIC: minimum inhibitory concentration; ROS; reactive oxygen species; SOD: superoxide dismutase.