A REVIEW ON CONSTITUENTS, PHARMACOLOGICAL ACTIVITIES AND MEDICINAL USES OF GLYCYRRHIZA GLABRA
Savita Pandey, Bipin Verma, Priti Arya
Department of Pharmacy, Government Polytechnic, Kashipur, Uttarakhand, India
*Corresponding Author’s Email: savitapharma@gmail.com
DOI: http://doi.org/10.22270/ujpr.v2i2.RW2
Plants have been one of the important sources of medicines for human being and animals since the ancient time. At present scenario there is an increasing demand for herbal medicines, health products and pharmaceuticals products. Herbal medicines have attained popularity at global level to replace the synthetic chemicals as they have shown less adverse reactions.
Glycyrrhiza glabra Linn is a commonly used herb for different diseases. Present review article deals with chemical constituents present in various parts of Glycyrrhiza glabra and pharmacological activities. Present article aim to comply all the updated information on its phytochemical and pharmacological activities, which were performed by widely different methods. Glycyrrhiza glabra Linn possesses antibacterial, antioxidant, antimalarial, antispasmodic, anti-inflammatory and anti-hyper glycemic properties. Various other effects like antiulcer, antiviral, antifungal have also been discussed. This article may be useful for many researchers in discovering potential therapeutic effects and developing new formulations.
Keywords: Antibacterial, anti malarial, antioxidant, Glycyrrhiza glabra, glycyrrhizin.
INTRODUCTION
Human beings have used plants for medicinal purposes for centuries. It has been estimated that such use of medicinal plants possibly go back in time to around 3000 years. Today, a great percentage of the world population, particular in developing countries, uses plants for facing primary needs of medical assistance1. Modern drugs like aspirin, atropine, ephedrine, digoxin, morphine, quinine, reserpine and tubocurarine are examples, which were originally discovered through observations of traditional cure methods of indigenous people2.
Glycyrrhiza glabra has been known in pharmacy for thousands of years. In old Chinese pharmacy, it was considered to belong to drugs of the first class and to it was ascribed the rejuvenating property when consumed for long periods3. In ancient Egypt, Greece and Rome licorice was frequently used. The earliest record of its use in medicine is found in “code Humnubari” (2100 BC)4. It was also one of the important plants mentioned in Assyrian herbal (2000 BC). Hippocrates (400 BC) mentioned its use as a remedy of ulcers and quenching of thirds. The drug was also mentioned by Theophrastus and Dioscorides. In traditional Siddha system of medicine, liquorice is used as a demulcent, expectorant, anti-tussive, laxative and sweetener5.
DISTRIBUTION/ HABITAT
This plant is cultivated in Russia, UK, USA, Italy, France, Germany, Spain, China and Northern India (Punjab and Sub-Himalayan tracts). It is distributed in Southern Europe, Syria, Iran, Afghanistan, Russia, China, Pakistan and Northern India. Large scale commercial cultivation is seen in Spain, Sicily and England10.
Table 1: Classification
Kingdom |
Plantae |
Subkingdom |
Tracheobionta-Vascular plants6 |
Super division |
Spermatophyta-Seed plants |
Division |
Magnoliophyta |
Class |
Magnoliopsida7 |
Subclass |
Rosidae |
Order |
Fabales8 |
Family |
Fabaceae-Pea family |
Genus |
Glycyrrhiza licorice9 |
Species |
Glycyrrhiza glabra L |
CULTIVATION
It is a perrineal herb/ sub shrub for subtropical and temperate zone. Young pieces of stolons having 2-3 buds of aerial shoot are used for propagation. Three to four feet deep soil having light, loamy, stone-free texture is needed for the plant11. It is usually grown continuously on the same land. Licorice enjoys fertile, sandy or clay soil near a river or stream where enough water is available for the plant to flourish in the wild, or under cultivation where it can be irrigated.
The pieces of stolons are planted in March at 2' by 3' distance. The plant attains a maximum height up to 2 m. The underground stem grow horizontally up to 2 m length, highly branched consisting of short taproot with large number of rhizomes12. The roots are harvested 3-4 years after planting when they show sufficient growth. Dry conditions at planting time and for the next two months give best chance for a good crop. A yield of two tons of roots per acre for bailing, plus 3-4 cwt of trimmings or offal is considered satisfactory. Rhizomes and roots are dug up in October, from the plants which have not borne the fruits. Drug is washed after removal of buds and rootlets. Some pieces are peeled and divided into small pieces. The drug is dried first under sun and then in shades, during which it loses about 50 per cent of its weight13.
MORPHOLOGY
Leaves- are compound, imparipinnate, alternate, having 4-7 pairs of oblong, elliptical or lanceolate leaflets covered with soft hairs on underside.
Flowers- are narrow, typically papilionaceous, axillary spikes, lavender to violet in color. The calyx is short, campanulate, with lanceolate tips and bearing glandular hairs14.
Fruit- is a compressed legume or pod, upto 1.5 cm long, erect, glabrous, somewhat reticulately pitted, and usually contains, 3-5 brown, reniform seeds15.
Root- is approximately 1.5 cm long and subdivides into subsidiary roots, about 1.25 cm long, from which the horizontal woody stolons arise. They may reach 8 m and when dried and cut, together with the root, constitute commercial licorice. It may be found peeled or unpeeled. The pieces of root break with a fibrous fracture, revealing the yellowish interior with a characteristic odor and sweet taste16.
CHEMICAL CONSTITUENTS
Flavonoid rich fractions include liquirtin, isoliquertin liquiritigenin and rhamnoliquirilin and five new flavonoids-glucoliquiritin apioside, prenyllicoflavone A, shinflavanone, shinpterocarpin and 1- methoxyphaseolin isolated from dried roots. The roots of Glycyrrhiza glabra Linn contain glycyrrhizin, which is a saponin that is 60 times sweeter than cane sugar. Both glycyrrhizin and glycyrrhetic acid can exist in the 18α and 18β stereoisomers17. Isolation and structure determination of licopyranocoumarin, licoarylcoumarin, glisoflavone together with a new coumarin-GU-12 are also reported. Four new isoprenoid-substituted phenolic constituents-semilicoisoflavone B, 1-methoxyficifolinol, isoangustone A, and licoriphenone had isolated from roots18. Also a new prenylated isoflavan derivative, kanzonol R was also isolated19.
The presence of many volatile components such as pentanol, hexanol, linalool oxide A and B, tetramethyl pyrazine, terpinen-4-ol, α-terpineol, geraniol and others in the roots are also reported. In addition presence of propionic acid, benzoic acid, ethyl linoleate, methyl ethyl ketine, 2, 3-butanediol, furfuraldehyde, furfuryl formate, 1-methyl-2- formyl pyrrole, trimethyl pyrazie, maltol and other compounds are also isolated from the essential oil.
Table 2: Quantitative standards
Total ash |
Not more than 4.5 % |
Acid insoluble ash |
Not more than 1.5% |
Water soluble ash20 |
Not more than 1% |
Aqueous extractive value |
Not less than 20% |
Ethanolic extractive value |
Not less than 15% |
Chloroform extractive value21 |
Not less than 5% |
Water soluble extractive |
Not less than 20% |
Moisture content22 |
Not more than 7.45% |
Pharmacology
After oral administration of licorice in humans, the main constituent, glycyrrhizic acid, is hydrolyzed to glycyrrhetic acid by intestinal bacteria possessing a specialized ß-glucuronidase. Glycyrrhetic acid is 200-1,000 times more potent an inhibitor of 11-ß-hydroxysteroid dehydrogenase (involved in corticosteroid metabolism) than glycyrrhizic acid23. After oral dosing, glycyrrhetic acid is rapidly absorbed and transported via carrier molecules to the liver. In the liver it is metabolized to glucuronide and sulfate conjugates, which are subsequently rehydrolyzed to glycyrrhetic acid24. Glycyrrhetic acid is then reabsorbed, resulting in a significant delay in terminal clearance from plasma. In the 24-hour period after oral administration, glycyrrhizin was found in the urine, indicates it’s partly absorption as an intact molecule25.
TRADITIONAL USES
PHARMACOLOGICAL ACTIVITIES
The liquorice powder and extract were found to be effective in the treatment of sore throat, cough and bronchial catarrh. Liquorice has been shown to work as efficiently as codeine in sore throat. It decreases irritation and produces expectorant effects. Carbenoxolone (a semi synthetic compound derived from Glycyrrhiza) stimulates gastric mucus secretion. Glycyrrhizin is responsible for demulcent action of liquorice. Liquiritin apioside, an active compound present in the methanolic extract of liquorice which inhibits capsaicin induced cough30.
Glycyrrhiza have a significant free-radical quenching effect. Liquorice flavonoids have exceptionally strong antioxidant activity. Antioxidant activity of liquorice flavonoids was found to be over 100 times stronger than that of antioxidant activity of vitamin E. Thus, liquorice extract can be efficiently used to formulate cosmetic products for the protection of skin and hair against oxidative damage31, 32.
Licochalcone A (a chalcone) present in liquorice is responsible for antimalarial activity. A previous reported study against P. yoelii in mice with oral doses of 1000 mg kg-1 have shown to eradicate malaria parasite completely33.
Glycyrrhiza glabra possess good anti fungal activity. In a previous reported study of screening for antifungal compounds from various plant materials, licorice extract with 80% methanol (oil-based extract of licorice; OEL) was found to possess high fungicidal effect against Arthrinium sacchari M001 and Chaetomium funicola M002 and its active compound was identified as glabridin34. Thus, liquorice extract has a great potential in formulating cosmetic products with antiseptic activities.
A studies proved that Glycyrrhiza glabra at 100μg/ml concentration, possess immunostimulatory effects. It increases production of TCD69 lymphocytes and macrophages from human granulocytes. In a previous reported study, liquorice root extract was found to prevent the rise in the amount of immune-complexes related to autoimmune diseases like systemic lupus erythematosus35.
Glycyrrhizinic acid, a major component of licorice, has antiulcer effect by raising the local concentration of prostaglandins that promote mucous secretion and cell proliferation in the stomach. In a previous reported study activity of Extractum liquiritiae (EL), glycyrrhizic acid, glycyrrhetinic acid and a novel lipophilic derivative of glycyrrhetinic acid monoglucuronide (GAMG), acetylated GAMG(aGAMG), were active against 29 Helicobacter pylori strains. The potent in vitro activity of glycyrrhizic acid against H. pylori concludes its beneficial effect on peptic ulcers36.
In a previous reported study ethanolic (95%) extract of root of Glycyrrhiza glabra and its fractions were investigated for its antidyslipidaemic activity on dyslipidaemic hamsters.
The reduction in LDL-cholesterol level by ethanolic extract, ethyl acetate soluble fraction and water soluble fraction were 43.9, 31.0, 33.4 and 24.6%, respectively. The treatment with Glycyrrhiza glabra root ethanolic extract and its fractions significantly brought down LDL and VLDL in the HFD fed hamsters to various degrees37.
Secondary metabolites such as; saponins, alkaloids and flavonoids present in hydro-methanolic root extract of Glycyrrhiza glabra, possess potent antibacterial activity against Staphylococcus aureus. Moreover various studies on aqueous and ethanolic extracts of liquorice proved its inhibitory activity on cultures of Staphylococcus aureus and Streptococcus pyogenes38.
It is reported that liquorice extract inhibits the growth of viruses, including herpes simplex, Varicella zoster, Japanese encephalitis, influenza virus, vesicular stomatitis virus and type A influenza virus. Glycyrrhizin does not allow the virus cell binding. Thus, it is found to have a prominent antiviral activity39.
In a previous reported study the in-vivo effects Glycyrrhiza glabra extract and combined effect with Vitamin K and Heparin were evaluated in Sprague Dawley Rats. It is found that extract of G.glabra increased the bleeding time when given in the doses of 180 mg/kg and 360 mg/kg. Blood loss was evaluated 60 minute later as a function of absorbance at 540 nm due to hemoglobin content in water solution. Altogether data indicates that Glycyrrhiza glabra is an effective anti thrombotic agent40.
Liquorice has a significant hair growth activity and it can be safely used in herbal formulations in treatment of various types of Alopecia. In a previous reported study hydro-alcoholic extract of liquorice showed good hair growth promoting activity. Comparison between liquorice extract and the standard drug used (Minoxidil 2%) showed that, 2% concentration of liquorice extract showed better hair growth stimulatory activity than 2% Minoxidil41.
The extract of liquorice is reported to be an effective pigment lightening agent. Glabridin in the hydrophobic fraction of liquorice extract inhibits tyrosinase activity in cultured B16 murine melanoma cells. Some other active compounds in liquorice extract like glabrene, Licochalcone A, Isoliquiritin are also responsible for inhibition of tyrosinase activity. Liquiritin present in liquorice extract disperse melanin, thereby inducing skin lightening42.
It is reported that glycyrrhetinic acid in liquorice extract gives anti-inflammatory effect similar
to glucocorticoids and mineralocorticoids Liquorice root (Glycyrrhiza) extract promotes the healing of ulcers of the stomach and mouth and this fact was known for over 2000 years.
According to studies, glycyrrhizic acid inhibits all factors responsible for inflammation. It inhibits cyclooxygenase activity and prostaglandin formation. It is also responsible for indirectly inhibiting platelet aggregation43.
In a previous study Kuroda M et al. reported that ethyl acetate extract of licorice exhibited a
significant PPAR-γ (peroxisome proliferator-activated receptors) that function as transcription factors regulating the expression of genes involved in glucose and lipid metabolism binding activity. Finally reduces the blood glucose level in knockout diabetic mice44
Glycyrrhizin induced a significant reduction in serum aminotransferases and improved the liver histology45. It has also been implicated that long-term usage of glycyrrhizin prevents development of hepatocellular carcinoma in chronic hepatitis C. In vitro studies have indicated that glycyrrhizin modifies the intracellular transport and suppresses hepatitis B virus (HBV) surface antigen (HbsAg)46.
CONCLUSION
At present scenario there has been an increase in demand for the phytopharmaceuticals all over the world because of the fact that the allopathic drugs have more side effects. This forms a basis for the selection of plant for further phytochemical and pharmacological investigation.
The pharmacological activities reported in the present review confirm the therapeutic value of Glycyrrhiza glabra. The plant has been used since centuries for asthma, bronchitis, ulcers, and an anti-inflammatory. It is reported to contain essential oil, coumarins, alkaloids and flavonoids. Extract of root can be found in various herbal preparations that are in market
today. Presence of chemical compounds indicates that the plant could serve as “lead” for development of novel agents for disorders in the coming years.
In this regard, further studies need to be carried out to explore Glycyrrhiza glabra Linn for its potential in preventing and treating diseases. So, the present review gives a direction for future investigators to carry out research on the plant so that they could get some medicinally important drugs or may design new dosage form of active constituents.
REFERENCES
Figure 1: Leaves, flower, root and powder of Glycyrrhiza glabra
Figure 2: Chemical structure of some active constituents of Glycyrrhiza glabra