Licorice commonly known as Y ashthimadhu in Ayurveda is one such plant. Licorice (Glycyrrhiza glabra) symbolises all that is wondrous in nature because, the it is used as traditional medicine for household remedy against various human ailments from antiquity. Licorice is a very well-known herb in Chinese medicine. In China, it is called “gancao” means sweet grass and has been recorded in the Shennong's classic of Materia Medica around 2100 BC. which says that licorice was supposed to have life-enhancing properties. It was used to have the functions of nourishing, alleviating pain, eliminating phlegm, and relieving coughing. The canvas of the pharmacological activities when complied it stands out strongly as  a  drug of choice  in  various disorders.  Licorice contains more than 20 triterpenoids and nearly 300 flavonoids. Among them, glycyrrhizin (GL), 18-beta-glycyrrhetinic (GA), liquiritigenin (L TG), licochalcone A (LCA, licochalcone E (LCE) and glabridin (GLD) are main active components which possess  antimicrobial and  anti  viral activities. 

Antibacterial activity of glycyrrhiza glabra on oral pathogens showed that glycyrrhiza glabra extract showed good antibacterial activity against six bacterias includingStreptococcus mutans, Actinomyces viscous, E coli, Streptococcus aureus and Streptococcus sanguis.  Twice daily use of herbal liquorice lollipop significantly reduced, the number and relative percentage of S mutans in high-risk children for 22 days which then stabilized and begin to rebound. An unusual biflavonoid named licoagrodin was isolated from the hairy root cultures of G. glabra along with three prenylatedretrochalcones, licoagrochalcones B, C, D, a prenylatedaurone, licoagroaurone and four known prenylated flavonoids, licochalcone C, kanzonol Y, glyinflanin B and glycyrdione A. From the glycosidic fraction, aisoflavone glycoside, licoagroside A, and a maltol glycoside, licoagroside B were isolated together with four known isoflavone glycosides, two flavone C-glycosides, and three other glycosides.  The isoflavonesglabridin and hispaglabridins A and B had antioxidant activity and both glabridin and glabrene possessed estrogen like activity.

In traditional Chinese medicine, the plant is recommended as a common remedy for gastrointestinal problems, cough, bronchitis, and arthritis. In particular, it is still widely used to treat gastritis, peptic ulcers, respiratory infections, and tremors in folk medicine. Commonly, G. glabra root is employed to prepare a tea that is an excellent thirst quencher. The dried root has been described as a tooth cleanser. Actually, the most important industrial use of G. glabra is the production of food additives, such as flavours and sweetening agents. In particular, the root is used as a flavouring agent for American‐type tobacco, chewing gum, candies, baked goods, ice cream, and soft drinks. Nutritionally, liquorice is a source of proteins, amino acids, polysaccharides and simple sugars, mineral salts (such as calcium, phosphorus, sodium, potassium, iron, magnesium, silicon, selenium, manganese, zinc, and copper), pectins, resins, starches, sterols, and gums. Oestrogens, tannins, phytosterols (sitosterol and stigmasterol), coumarins, vitamins (B1, B2, B3, B5, E, and C), and glycosides have been reported. A large number of biological compounds have also been isolated, mostly triterpenes, saponins (responsible for the sweet taste), and flavonoids. The main constituent of roots is glycyrrhizin, a triterpenoid sapo-nin that is almost 50 times sweeter than sucrose, being the primary active ingredient. Glycyrrhizin represents about 10% of the liquorice root dry weight, being a mixture of potassium, calcium, and magnesium salts of glycyrrhizic acid that varies between 2% and 25%. After oral administration, glycyrrhizin is metabolized to 18‐glycyrrhetic acid 3‐ omonoglucuronide and glycyrrhetic acid by intestinal bacteria. Liquiritin apioside, an active compound reported in the methanolic extract of liquorice, has the ability to inhibit capsaicin, a compound that induces cough. The effect on sore throat has been compared with that of carbenoxolone, a glycyrrhetinic acid derivative with a steroid‐like structure, which stimulates gastric mucus secretion.

Another accession, EC-21950, has been identified by All India Coordinated Research Project on Medicinal and Aromatic Plants; this variety is also tolerant to the root rot disease. Other varieties of mulethi are EC-114303 and EC-124587 (Zaidi, 2011). The crop remains in the field for two and a half to three years, every year the same dose has to be applied (Farooqi, 2001). The yield of mulethi depends upon the soil fertility, variety of plant, climatic conditions and method of cultivation. A yield of 5 tons of roots and 14-20 tons of trimming is considered satisfactory. The HM-1 yields 7-8 tons roots with a 7.5 per cent content of glycyrrhizin (Uniyal  and Jariyal, 2003). Licorice commonly known as Y ashthimadhu in Ayurveda is one such plant. Licorice (Glycyrrhiza glabra) symbolises all that is wondrous in nature because, the it is used as traditional medicine for household (Korhalkar et al, 2014) remedy against various human ailments from antiquity. Licorice is a very well-known herb in Chinese medicine.   In China, it is called “gancao” means sweet grass and has been recorded in the Shennong's classic of Materia Medica around 2100 BC. which says that licorice (Wang and Liu, 2015) was supposed to have life-enhancing properties.  It was used to have the functions of nourishing, alleviating pain, eliminating phlegm, and relieving coughing. The canvas of the pharmacological activities when complied it stands out strongly as a drug of choice in various (Korhalkar et al, 2014) disorders. Licorice contains more than 20 triterpenoids and nearly 300 (Wang and Liu, 2015) flavonoids. Among them, glycyrrhizin (GL), 18-beta-glycyrrhetinic (GA), liquiritigenin (L TG), licochalcone A (LCA, licochalcone E (LCE) and glabridin (GLD) are main active components which (Lingaraj et al, 2014) possess antimicrobial and anti viral activities. 

Sedighinia et al. (2012) conducted an in vitro study to analyse antibacterial activity of glycyrrhiza glabra on oral pathogens which showed that glycyrrhiza glabra extract showed good antibacterial activity against six bacterias including Streptococcus mutans, Actinomyces viscous, E coli, Streptococcus aureus and Streptococcus sanguis.  Sug et al. (2012) conducted an in vitro study to analyze  the  antimicrobial effects  of deglycyrrhizinated  licorice  root extract  (DG-LRE)  on streptococcus mutans UA159 in both planktonic and biofilm cultures and concluded  that  it  has  strong antimicrobial  activity  against S  mutans in  planktonic phase. Peter et  al. (2010) concluded  that  twice daily use of herbal liquorice lollipop  significantly  reduced, the  number  and relative percentage of S mutans in high-risk children for 22 days which then stabilized  and  begin to  rebound.  Jain et al. (2013) showed  that  highest number  of  fall in  streptococcus  mutans colony counts was observed in  ethanolic liquorice  group and at the  same time palatable  by  child patients. 

Vu Dang et al. (2011) reported that LIAand LC inhibited the secretion of interleukin 6 and chemokine in a dose dependent manner and hence can have potential for the development of novel host modulating Strategies for the treatment of cytokinin and MMP mediated disorders such as periodontitis.  Farhad et al.  (2013) resulted that the decrease in mean MMP 8 concentration was higher in doxycline  and  liquorice group  in  comparison with the  placebo  group and concluded  that  licorice extract  can  prevent the  production  of  MMP by  host cell  and  can be  useful  as antibiotic  like  doxicycline to  cure peridontitis  and other  inflammatory  diseases, with  no  side effects.  In  a study  by  Geetha and  Anitha (2013) on  in vitro  evaluation  of antimycotic  activity of  ethanolic  extract of  Glycyrrhiza  glabra, the  results clearly indicated the antifungal activity of ethanolic extract of glycyrrhiza  glabra  on organisms  like  candida albicans,  aspergillus  fumigates, aspergillus  Niger,  mucus species and  Penicillium  marneffei which  could  be enhanced  with  purified active  components  and determined  adequate dose  for  proper administration. An in vitro and in  vivo  study conducted  by  Seleem   et  al. (2016)   to check  the  antifungal activity  of  Lichochalcone –A  against  candida albican  biofilm. Lichochalcone –Ais a bio active natural compound found in licorice root.   The result  of   the study showed that   625µM Lichochalcone –A significantly reduced biofilm growth compared to control group by reducing colony forming units and reducing activity of proteolytic enzymes. Messeier et al. (2012) in  the article  on Licorice and  its potential beneficial  effects  in common  orodental  diseases stated  that  liquorice and  its bioactive ingredients  such as  glycyrrhizin, glabidin, licochalcone A, licoricidin  and  licorisoflavan  A possesses  potential  beneficial effects  in oral  diseases including  recurrrent  aphthous ulcer.  Rafi et al. (2012) stated that novel polyphenols molecule isolated from liquorice  root induces  apoptosis,  G2/M cycle  arrest,  and BCL-2 phosphorylation  in  tumor cell  lines.  Sinha   and Sinha (2014)  stated  that liquorice  has  shown greater biocompatibility with fibroblast cells compared to  calcium hydroxide, which  is severely  toxic  to cells.  Hence a  mixture of  liquorice  and Calcium Hydroxide  can  be used  to  minimize toxicity  to  fibroblasts. Kim et  al. (2018) conducted  a study  to  analyze the  anti-inflammatory effects of licorice and roasted  licorice of    extracts on 12- O-tetradecanoylphorbol-13-acetate (TP A)  induced  acute inflammation and  collagen induced arthritis in mice and suggested supplementation with  licorice  extract (LE)  and  roasted licorice  extract (rLE) may be beneficial in  preventing and both acute and  chronic  inflammatory conditions  like  arthritis.A yield of two tons of roots per acre for bailing, plus 3-4 cwt of trimmings is considered satisfactory (Chopra and Chopra, 2006). Root-T.S showed structure of closely resembling that of stolon except that no medulla was present; xylem tetrarch; usually four principal medullary rays at right angles to each other; in peeled drug cork showed phelloderm and sometimes without secondary phloem; all parenchymatous tissues had abundant, simple oval or rounded starch grains, 2-20µ in length. Glycyrrhizin is a nonhemolytic saponin with foaming property (Vispute and Khopade, 2011). To produce these quantities of active principles, 300 tons of Glycyrrhiza roots will be required. It could be cultivated on waste/marginal lands (Shinwari et al, 2003). An unusual biflavonoid named licoagrodin was isolated from the hairy root cultures of G.. glabraalong with three prenylatedretrochalcones, licoagrochalcones B, C, D, a prenylatedaurone, licoagroaurone and four known prenylated flavonoids, licochalcone C, kanzonol Y, glyinflanin B and glycyrdione A. From the glycosidic fraction, aisoflavone glycoside, licoagroside A, and a maltol glycoside, licoagroside B were isolated together with four known isoflavone glycosides, two flavone C-glycosides, and three other glycosides (Li et al, 2000). The isoflavonesglabridin and hispaglabridins A and B had antioxidant activity and bothglabridin and glabrene possessed estrogen like activity (Kataria et al, 2013). The decoction of the root is a good wash for falling and graying hair (Singh et al., 2006). Large randomized placebo-controlled trials on humans conducted by Upjohn Company for minoxidil, a potassium channel opener, showed efficacy in 54 % of the treated patients compared to 34 % in placebo (control) group. Thus, minoxidil (reference) was a more effective hair growth enhancer than the control group but was inferior to the 2% extract-treated group probably due the fact that G. glabraextract has some estrogenic property (Somjen et al, 2004). A recent study on Eclipta albaherb which validate it as a hair growth promoter showed that thepresence of antigen FGF-7 and Shh and absence of BMP4 favoured anagenic state of hair (Dattaa et al, 2009). The extracts are currently used in pharmaceutical and food industries, as well as in the manufacture of functional foods and food supple-ments (Hayashi & Sudo, 2009; Herrera et al, 2009).

The use of liquorice predates the Greek and Roman empires, hav-ing a long history of traditional medicines and folk remedies. In fact, different geographical areas and periods are linked to different uses (Armanini et al, 2002). The first documents can be traced back to ancient Assyrian, Egyptian, Chinese, and Indian cultures. Theophrastus and Pedanius Dioscorides wrote about liquorice as a medicinal plant and described its therapeutic effects (Armanini et al, 2002). In traditional Chinese medicine, for example, the plant is recommended as a common remedy for gastrointestinal problems, cough, bronchitis, and arthritis. In particular, it is still widely used to treat gastritis, peptic ulcers, respiratory infections, and tremors in folk medicine. Commonly, G. glabra root is employed to prepare a tea that is an excellent thirst quencher. The dried root has been described as a tooth cleanser (Armanini et al., 2002). Actually, the most important industrial use of G. Glabra is the production of food additives, such as flavours and sweetening agents (Mukhopadhyay & Panja, 2008). In particular, the root is used as a flavouring agent for American‐type tobacco, chewing gum, candies, baked goods, ice cream, and soft drinks (Rizzato et al, 2017). With regard to government approval, liquorice extract and glycyrrhizin have been allowed for use in foods by the United States Food and Drug Administration, the Council of Europe, and the Joint FAO/WHO Expert Committee on Food Additives (FAO, 2005). The genus Glycyrrhiza (Fabaceae) consists of about 30 species, such as G. glabra, G. uralensis, G. inflata, G. aspera, G. korshinskyi, or G. eurycarpa. Like the other plants of Fabaceae, G. glabra is able to fix nitrogen, due to symbiosis with bacteria of the genus Rhizobium, at the root level, being suitable for sandy and clay soils, though preferring humid soils. Since the Egyptian age, the therapeutic proper-ties of G. glabra are well documented (Fiore et al, 2005). The roots are the most used parts whereas leaves are considered an agrochemical waste. However, in the last years, different authors studied the phytochemical composition of G. glabra leaves, demonstrating that certain compounds present in the roots are also identified in leaves, although in smaller quantities (Hayashi & Sudo, 2009; Siracusa et al, 2011).

In the last years, the chemical constituents of liquorice have been extensively investigated by different authors (Hayashi et al, 2016; Siracusa et al, 2011). Nevertheless, few studies were carried out on the nutritional composition of G. glabra. Nutritionally, liquorice is a source of proteins, amino acids, polysaccharides and simple sugars, mineral salts (such as calcium, phosphorus, sodium, potassium, iron, magnesium, silicon, selenium, manganese, zinc, and copper), pectins, resins, starches, sterols, and gums (Wang et al, 2015). Oestrogens, tannins, phytosterols (sitosterol and stigmasterol), coumarins, vitamins (B1, B2, B3, B5, E, and C), and glycosides have been reported (Wang et al, 2015). A large number of biological compounds have also been isolated, mostly triterpenes, saponins (responsible for the sweet taste), and flavonoids (Rizzato et al, 2017; Wang et al, 2015). The main constituent of roots is glycyrrhizin, a triterpenoid sapo-nin that is almost 50 times sweeter than sucrose, being the primary active ingredient (Yu et al, 2015). Glycyrrhizin represents about 10% of the liquorice root dry weight, being a mixture of potassium, calcium, and magnesium salts of glycyrrhizic acid that varies between 2% and 25% (Rizzato et al., 2017). After oral administration, glycyrrhizin is metabolized to 18‐glycyrrhetic acid 3‐ omonoglucuronide and glycyrrhetic acid by intestinal bacteria (Albermann et al, 2010).

Glabridin is the principal isofla-vone identified, ranging between 0.08% and 0.35% of roots' dry weight (Simmler et al., 2013). The minor phenolic compounds are isoprenoid‐substituted flavonoids, chromenes, coumarins, dihydrostilbenes, coumestans, benzofurans, and dihydrophenanthrenes. Furthermore, many volatile components are present in roots, such as geraniol, pentanol, hexanol, terpinen‐4‐ol, and α‐terpineol, conferring the characteristic odour. The essential oil obtained fromG. glabrais also rich in propionic acid, benzoic acid, furfuraldehyde, 2,3‐butanediol, furfuryl formate, maltol, 1‐methyl‐2‐formylpyrrole, and trimethylpyrazine (Chouitah et al, 2011) The phenolic content is probably responsible for the powerful antioxidant activity observed (Rackova et al, 2007). Varsha and Sonam (2013) attributed this activity to flavonoids, whereas Singh et al. (2015) reported that mostly isoflavones, such as glabridin, hispaglabridin A, and 30‐hydroxy‐4‐O‐methylglabridin, are the responsible compounds. Biondi et al. (2003) reported a huge antioxidant activity of the dihydrostilbene derivates present inG. Glabra leaves. Also, licochalcones B and D are present in G. glabra, showing a strong scav-enging activity on DPPH radical and the ability to inhibit the micro-somal lipid peroxidation (Biondi et al, 2003; Sharma et al, 2016). According to Castangia et al. (2015), the topical application of liquorice extract for-mulations may be of value in innovative dermal and cosmetic products as it counteracts oxidative stress damage, maintaining the skin homeo-stasis due to its high antioxidant content.

The anti‐inflammatory activity of G. glabraand its use in the treat-ment of inflammatory diseases have been documented since ancient times (Yang et al, 2017). Shalaby et al. (2004) evaluated the anti‐inflammatory activity of G. glabra in male rats after 4 weeks of food intake. The authors observed a significant decrease in the total cholesterol and triglyceride levels as well as in the levels of serum liver enzymes. Harwansh et al. (2011) reviewed the pos-itive effects of G. glabraon the treatment of the upper respiratory tract and gastric system diseases. These pharmacological effects were due to an increase in the secretion of serotonin and prostaglandins in the stomach that led to a decrease of gastric inflammation (Bahmani et al, 2014). Different authors described that the anti‐inflammatory action is primary mediated by glycyrrhizin, which in vitro could inhibit factors responsible for inflammation as well as promote the healing of stomach and mouth ulcers (Rackova et al, 2007; Yin et al, 2017). Furthermore, G. glabra is used in renal and liver complications on the basis of its strong anti‐ inflammatory effects (Xiao et al, 2010). Xiao et al. (2010) reported the inhibition of liver granuloma formation and the inflammatory cytokine production by glycyrrhizin, whereas Wang et al. (2017) described the anti‐inflammatory effects on endometriosis. Moreover, Liu et al. (2017) proved the anti‐inflammatory activity of glabridin on RAW cells.

The antitussic and expectorant effects of liquorice have been reported by different authors, particularly its useful effects on the treatment of sore throat, cough, and bronchial catarrh (Damle, 2014; Fiore et al, 2005). These effects are associated with the presence of glycyrrhizinthat helps to expel congestion in the upper respiratory tract and accel-erates tracheal mucus secretion (Sharma et al, 2016). Likewise, liquiritin apioside, an active compound reported in the methanolic extract of liquorice, has the ability to inhibit capsaicin, a compound that induces cough (Kamei et al, 2003). The effect on sore throat has been compared with that of carbenoxolone, a glycyrrhetinic acid derivative with a steroid‐like structure, which stimulates gastric mucus secretion (Damle, 2014).

The use of G. glabra extract as antiulcerative is widely known. For the gastrointestinal system, it is used in gastric and duodenal ulcers, whereas for the treatment of spasmodic pains of chronic gastritis, it is employed as an adjuvant (Armanini et al, 2002). The benefits o f G. Glabra in the treatment of duodenal and peptic ulcers has been reported since the 1970s, and this traditional use is related to the presence of anti‐ inflammatory saponins (Krausse et al, 2004). The major compound responsible for this activity is glycyrrhizin, which can raise the concen-tration of prostaglandins in the digestive tract, promoting stomach mucus secretion (Jafarian & Ghazvini, 2007). In addition, liquorice prolongs the lifespan of stomach surface cells, demonstrating an antipepsin effect (Ram et al, 2010). Fur-thermore, deglycyrrhizinated liquorice has shown some effects in the treatment of gastrointestinal ulcers, suggesting the presence of other active ingredients (Zadeh et al, 2013). Indeed, carbenoxolone, a glycyrrhetinic acid analogue, is reported to inhibit two important enzymes for the metabolism of prostaglandin, 15‐hydroxyprostaglandin dehydrogenase and Δ 13 prostaglandin reductase, raising prostaglandin levels and leading to positive effects in clinical trials for gastric and duodenal ulcers (Damle, 2014). Different authors reported the antimicrobial properties of G. glabra, particu-larly on Gram‐positive and Gram‐negative bacteria such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Bacillus subtilis (Gupta et al, 2008; Wang et al, 2015). The antibacterial activity observed is due to the presence of secondary metabolites, namely, saponins, alkaloids, and flavonoids (Wang et al, 2015). 

Glabridin 75 mg/kg In vivo—oral administration to mice Decrease of MIP 1α[removed]Xiao et al., 2010) Glycyrrhizin 1–100μM DPPH, AAPH Protection against lipid peroxidation of liposomal membraneInhibition of ROS(Rackova et al., 2007) 50–200μg/ml LPS inflammatory mediators production (TNF‐α,IL‐1β,COX‐2, PG2) Decrease of endometriosis (Wang, et al, 2017) 10, 20, 100 mg/kg In vivo—mice Decrease of LPS inflammatory mediators (Yin et al, 2017) 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 B, 40‐methylglabridin, and 3‐hydroxyglabrol, isolated from G. glabra, are responsible for this activity (Wang et al, 2015). The mechanism behind this could be the decrease of bacterial gene expression, the inhibition of bacterial growth, and the reduction of bacterial toxin production (Gupta et al, 2008; Wang et al, 2015). In 2014, Ahn et al. (2014) demon-strated that liquorice prevents bacterial caries caused byStreptococcus mutans and Streptococcus sobrinus. Likewise, in vitro studies proved that aqueous and ethanolic extracts of liquorice have an inhibitory activity on Streptococcus pyogenes (Fukai et al, 2002a, b; Wang et al, 2015). On the other hand, the ability to inactivate methicillin‐resistant S. Aureus (MRSA) by decreasing the expression of SaeR and Hla, the key virulence genes of MRSA, have also been reported by different authors (Fukai et al, 2002a, b; Wang et al, 2015). It is also suggested that licochalcone E could be used for chemical synthesis of novel anti‐S. aureuscompounds, reduc-ing the production of α‐toxin in both methicillin‐sensitiveS. Aureus and MRSA (Wang et al, 2015). Besides, α‐haemolysin is an important exotoxin in the pathogen-esis o f S. ureusi nfections (Berube & Bubeck Wardenburg, 2013). Liquiritigenin, one of the most active compounds of liquorice, demonstrated the capacity to prevent human lung cells (A549) from α‐haemolysin‐mediated injuries, by decreasing α‐ haemolysin production (Wang et al, 2015). Similarly, glabrin and glycyrrhetinic acid have shown antibacterial activity against S. aureus (Singh et al, 2015).

Different authors reported the antibacterial action of G. Glabra against Mycobacterium tuberculosis (Gupta et al, 2008), demonstrat-ing that glabridin is the responsible compound for this activity, instead of hispaglabridin B (Simmler et al, 2013). The antitubercular phenolic compounds were previously identified as licoisoflavone and licochalcone A (Chakotiya et al, 2017). In a mice lung infection model, G. glabrawas therapeutically active against multidrug‐resistant strain of P. aeruginosa (Chakotiya et al, 2016), and the hydro‐alcoholic extract led to a reduction of the micro-bial load in the blood, mainly due to the presence of stigmasterol, ergosterol, licochalcone, and glabridin (Chakotiya et al, 2017). The activity of G. glabra against Helicobacter pylorihas been also reported, as mentioned in the previous subsection (Krausse et al, 2004). According to Krausse et al. (2004), the compounds responsible for this activity are glabridin and glabrene. Cao et al. (2016) also reported that 18β‐glycyrrhetinic acid significantly attenuated the gas-tritis infection caused by H. pylori. Asha et al. (2013) found that the fla-vonoid glabridin exhibits activity against H. Pylori whereas glycyrrhizin did not present activity even at a concentration of 250μg/ml. These flavonoids also showed activity against H. pyloristrains resistant to clarithromycin and amoxicillin (Fukai et al., 2002a, b). The proba-ble mechanism behind these actions is the inhibition of the protein synthesis, DNA gyrase, and dihydrofolate reductase (Fukai et al, 2002a, b). Moreover, the liquorice polysaccharides also present activity against Porphyromonas gingivalis adhesion, which is of huge importance because no specific adhesion inhibitors have been described (Chinsembu, 2016). The antifungal activity of G. glabra is also detailed (Sato et al., 2000). Sato et al. (2000) reported that the methanolic extract of liquorice presents fungicidal activity against Arthrinium sacchariandChaetomium funicola, whereas glabridin was found to be the active compound responsible for the observed effects (Sato et al, 2000). In fact, isoflavonoids, such as glabridin, glabrol, and their derivatives, are responsible for the in vivo inhibition of Mycobac-terium smegmatis, Shigella, Salmonella, E. coli, S. mutans, and Lactobacillus acidophilus (Ajagannanavar et al, 2014). Recently, Chandra and Gunasekaran (2017) also proved the antifungal activity of crude meth-anolic extract of G. Glabra against Aspergillus niger. Different authors reported that C. Albicans is susceptible to liquorice extracts due to their richness in liquiritigenin, liquiritin, licochalcone A, and glabridin (Chandra & Gunasekaran, 2017; Lee et al, 2009; Singh et al, 2015). Nevertheless, according to Karahan et al. (2016), the antimicrobial activity could be influenced by the environmental conditions that may affect the chemical compound contents and the biological activity. Licochalcone A and glabridin present a therapeutic potential against C. albicans oral infections, whereas glycyrrhizic acid had no effect (Messier & Grenier, 2011; Moazeni et al, 2017). 

The antiviral activity of G. glabra extracts against different viruses has been reported, including herpes simplex, Varicella zoster, Japanese encephalitis, influenza, and vesicular stomatitis virus (Wang et al, 2015). Different studies have demonstrated that two triterpenoids are responsible for the antiviral activity reported: glycyrrhizin and 18β‐glycyrrhetinic acid (Wang et al, 2015). These compounds have the ability to inhibit virus gene expression and replication, decreasing the adhesion force and stress and reducing HMGB1 binding to DNA (Wang et al., 2015). Also, they can enhance host cell activities by blocking the degradation of IκB enzyme involved in the propagation of the cellular response to inflammation, activating T lymphocyte proliferation, and suppressing host cell apo-ptosis (Wang et al, 2015). The antiviral mechanisms of both compounds are similar, inhibiting the adsorption and penetration of the virus in the early steps of the replicative cycle. Nevertheless, Cinatl et al. (2003) reported that these active principles are less effective if added during the adsorption period than after virus adsorption. On the other hand, Soufy et al. (2012) found that glycyrrhizin has excel-lent immunostimulant properties and induces a synergistic effect with duck hepatitis virus (DHV) vaccine by activatingT lymphocyte proliferation. Thus, the treatment with glycyrrhizin alone or in combination with DHV vaccine could lead to an immune stimulation and antiviral effect against DHV (Soufy et al, 2012).

Herpes simplex virus (HSV) is one of the most common viruses infecting humans and animals. During HSV infection, the cellular adhe-sion is increased, playing a key role in inflammatory response. Huang et al. (2012) reported that the adhesion force and stress between the cerebral capillary vessel endothelial cells and the poly-morphic nuclear leukocytes were amplified during HSV infection. Glycyrrhizin stimulates the mouse defence system against HSV‐1 infection (Sekizawa et al, 2001). Furthermore, glycyrrhizic acid was found to have a distinctive effect against Kaposi sarcoma‐associated herpes virus (KSHV). It was proved that glycyrrhizic acid could terminate the latent infection of KSHV when all current drugs are ineffective (Damle, 2014). Also, glycyrrhizic aciddown‐regulates the expression of latency‐associated nuclear antigen in B lymphocytes leading to natural cell death (apoptosis) of the KSHV‐infected cells (Damle, 2014). Recently, the antiviral activity of glycyrrhizin against severe acute respiratory syndrome virus was eval-uated (Cinatl et al., 2003). Glycyrrhizin affects the cellular signaling pathways such as protein kinase C, casein kinase II, and transcription factors, namely, activator protein 1 and nuclear factor κB (Cinatl et al, 2003). Furthermore, glycyrrhizin and its aglycone, 18β‐ glycyrrhetinic acid, up‐regulate the expression of inducible nitric oxide synthase and the production of nitric oxide in macrophages (Cinatl et al, 2003). Zhang et al. also reported that glycyrrhizin reduces the expression of proinflammatory cytokines affecting coxsackievirus B3‐induced myocarditis (Wang et al, 2015; Zhang et al, 2012). Also, the activity against human immunodeficiency virus (HIV) was evaluated (Sasaki et al., 2002). Glycyrrhizin has been used to treat patients with HIV‐1 (Wang et al, 2015). The results revealed a low concentration of P24 antigen in patients, probably due to the up‐regulation of chemokines (Sabde et al, 2011).

Glycyrrhizin, when compared with the placebo, presents clinical interest for the possible treatment of chronic hepatitis C, inducing a significant reduction of the serum aminotransferases and an improvement in the liver histology (Ploeger et al., 2001). Intra-venous glycyrrhizin can be also used for the treatment of acute‐onset autoimmune hepatitis (Yasui et al., 2011). Another study shows that glycyrrhizin interferes with highly pathogenic H5N1 influenza A virus replication (Michaelis et al., 2011).Glycyrrhizin can also be used as a novel therapeutic method to control porcine epidemic diarrhoea virus (PEDV) infection, inhibiting the infection of Vero cells (namely, the entry and replication of PEDV) and decreasing the mRNA levels of proinflammatory cytokines (Huan et al, 2017). The hepatoprotective activity of glycyrrhizin and 18β‐glycyrrhetic acid by inhibition of free‐radical generation and lipid peroxidation has been extensively reported (Huo et al, 2011). One of these studies indicated that the hydromethanolic root extract ofG. Glabra exhibits a significant protection against hepatotoxicity induced by carbon tetrachloride in the liver tissue of mice (Sharma & Agrawal, 2017). The effects of liquorice on nonalcoholic fatty liver disease have also been investi-gated (Hajiaghamohammadi et al., 2012). According to Rizzato et al. (2017), glycyrrhizin and glycyrrhetinic acids prevent drug‐induced liver injury and ensure the disruption of bile acid metabolism in humans.

Indeed glycyrrhetinic acid has been reported as anti‐inflammatory and hepatoprotective compound (Yin et al, 2017). In addition, it prevents the oxidative and hepatic damage caused by aflatoxins through increasing CYP1A1 and glutathione‐S‐ transferase activity, contributing to the anticarcinogenic activity by metabolic deactivation of the hepatotoxin (Yang et al, 2017). Mahmoud et al. (2017) reported that the treatment with 18β‐glycyrrhetinic acid significantly reduced the serum enzymes, bilirubin, and proinflammatory cytokines in the liver, decreasing the expression of P450 E1. This activity is due to the 18β‐glycyrrhetinic and glycyrrhizic acids that induce mitochondrial permeability transition, leading to the apoptosis of tumour cells (Lee et al., 2008). Lee et al. (2008) demon-strated the toxic effect of G. glabraagainst the human cervix and uterus tumour cell line SiHa cells.  The hydromethanolic root extract of G. glabra also exhibited antimutagenic potential by sup-pressing micronuclei formation and chromosomal aberration in bone marrow cells of albino mice (Sharma et al, 2014). Glycyrrhizin and glycyrrhetinic acids are effective compounds in gastric cancer treatment, whereas glycyrrhizin suppresses throm-boxane A2 in lung cancer cell with low toxicity (Deng, et al, 2017). According to Wang et al. (2017), 18β‐ glycyrrhetinic acid has antitumour activities in breast and ovarian can-cer, gastric tumours, and leukaemia. In liver cancer, the compound inhibits the proliferation of HepG2 cells without affecting the normal liver cell line. In particular, 18β‐glycyrrhetinic acid increases the forma-tion of reactive oxygen species, nitric oxide production, and loss of the mitochondrial membrane potential (Hasan et al, 2016).

Glycyrrhetinic acid derivatives have also presented promising cytotoxicity on human breast cancer cell lines (MCF‐7, MDA‐MB‐ 231; Li et al., 2016). Also, the anticancer activity in human leukaemia, by inducing the apoptosis of HL‐60 cells through the activation of extrinsic and intrinsic apoptotic pathways, was proved by. Huang et al. (2016). Recently, licochalcone E, when compared with well‐known antitumour agents, licochalcone A and isoliquiritigenin, exhibited the most potent cytotoxic effect (. Xiao et al, 2011; Yu et al, 2017). Xiao et al. (2011) explored the licochalcone. A mechanism of action in MKN‐28, AGS, and MKN‐45 gastric cancer cells and human gastric epithelial immortalized cells (Park et al, 2015; Xiao et al, 2011). The results indicated that licochalcone A inhibits gastric cancer cells growth in a dose‐dependent way, by blocking cell cycle progression at the G2/M transition, inducing apo-ptosis. In addition, licochalcone A induced apoptosis by its effects on the expression of PARP, caspase‐3, Bcl‐2, and Bax (Xiao et al, 2011). Kanazawa et al. (2003) and Jung et al. (2006) showed that isoliquiritigenin inhibits the cell growth by G2/M cell cycle arrest inbreast and prostate tumour cells. 

Different studies demonstrated that isoliquiritigenin suppresses pulmonary metastasis in mice (Yamazaki et al, 2002) and human hep-atoma cells (Hsu et al., 2005). Apoptosis was primarily mediated through mitochondrial death cascade, as shown by loss of mitochon-drial membrane potential, release of cytochromec, and activation of caspase‐9. A possible explanation is that cell growth was arrested through up‐regulation of p53 and p21 and down‐regulation of cdk2, cyclin E, and E2F‐1 while apoptosis was induced by increasing Bax protein expression and activating caspase‐7 (Sharma et al, 2012). Glabridin exhibited antitumour properties in various human cancer cells (Jiang et al., 2016). The results revealed that glabridin induced apoptosis in dose dependently in Huh7 cells through caspase‐3, caspase‐8, and caspase‐9 activation and PARP cleavage (Hsieh et al, 2016).

The effects of G. glabra on learning and memory were investigated in mice (Dhingra & Sharma, 2006; Parle et al, 2004). In 2004, Parle et al. (2004) administered the extract of G. glabraorally to mice during 7 days at different concentrations (75–300 mg/kg). Chakravarthi and Avadhani (2013) and Dhingra and Sharma (2006) studied the effects of G. glabra root aqueous extract on the learning and memory of 1‐month‐old male Wistar albino mice at doses between 75 and 300 mg/kg, orally administered during six successive weeks. Both studies demonstrated a significant improvement of learning and mem-ory in mice, but the exact mechanism behind this action remains unknown (Chakravarthi & Avadhani, 2013; Dhingra & Sharma, 2006).