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Glycyrrhiza glabra: A Potent Herb from Traditional to Modern Medicine

Md Nasar Mallick*

Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, India

*Corresponding Author:
Md Nasar Mallick
Department of Pharmacy,
School of Medical and Allied Sciences,
Galgotias University,
Greater Noida,
India
E-mail:
 [email protected]

Received: 09-Mar-2022, Manuscript No. JPPS-22-56778; Editor assigned: 12-Mar-2022, PreQC No. JPPS-22-56778 (PQ); Reviewed: 25-Mar-2022, QC No JPPS- 22- 56778; Revised: 30-Mar-2022, Manuscript No. JPPS-22-56778(R); Published: 06-Apr-2022, DOI: 10.2320-0189.11.2. 001

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Abstract

Introduction: Glycyrrhiza glabra, an ayurvedic herb has had much medical importance since ancient times. It has anti-inflammatory action, anti-diabetic action, anti-viral, anti-cancer, expectorant as well as antitussive characteristics, antimicrobial, anti-ulcer, and hepatoprotective action. The primary medicinal components are the root, leaves, and rhizomes. Ayurvedic plants have possessed varieties of medicine values from ancient times, and Glycyrrhiza glabra has been chosen for evaluation based on its chemical components and pharmacological activity.

Methods: Methodology used to define the anti-inflammatory action, anti-diabetic action, anti-viral, anti-cancer, expectorant, antitussive characteristics, antimicrobial, anti-ulcer, and hepatoprotective action with a focus on Glycerrhiza glabra potential activity in various modern pathophysiological conditions.

Results: General pathophysiological aspects to target with Glycerrhiza glabra.

Discussion: The primary goal of the review is to demonstrate the various chemical components and pharmacological activity of Glycyrrhiza glabra with targeting various anti-inflammatory pathways like JACK-STAT, MAPK, COX2, and TXA-2 as well as anti-viral, anti-diabetic, expectorant and antitussive, anti-cancer, antimicrobial, anti-ulcer and hepatoprotective.

Introduction

A huge proportion of the population in underdeveloped nations uses plant products as medicine [1]. Glycyrrhiza glabra medicinal plants which been included in Ayurveda for a long time and have flavoring ingredients, and it is also known in English as Yashti-madhuka, licorice, and sweet food [2]. Glycyrrhiza is a Greek term that means "sweet root," and it is a soft and fibrous taproot that is used in medicine [3]. Sugar, resin, starch, asparagine, Glycyrrhetic acid, Glycyrrhizic acid, and Glycyrrhizin are all constituents of Glycyrrhiza glabra[4,5]. The root and rhizomes of Glycyrrhiza glabra have possessed medicinal activity such as an anti-inflammatory, antioxidant, antispasmodic, and expectorant [6]. It also has hepatoprotective properties. Glycyrrhiza glabra components such as Glycyrrhizin and Glabridin suppress neutrophils' production caused by reactive oxygen species where inflammation was caused [7]. The anti-oxidant in Glycyrrhiza glabra reduces the levels of NFkB, TNF-, and IL-17, all of which are implicated in the generation of inflammatory cytokines [8,9]. The major medicinal components are the leaves, roots, and rhizomes [10,11]. It also has laxative, contraceptive, and sexual enhancement properties[12]. Different biological active properties have been discovered in Glycyrrhiza glabra extract [13].

Literature Review

Components of Glycyrrhiza glabra

Different components containing water-soluble and Main biological compounds can be isolated from the root of the Glycyrrhiza glabra plant. These compounds include triterpenoid, glycosides, saponin, polysaccharides, tannins, essential oil, resins, proteins, steroids, and other different compounds [14,15]. Glycyrrhizin, which is roughly 60 times sweeter than sugar, is found in saponin. The dried root contains flavonoid components such as liquid, isoliquertin, liquiritigenin, rhamnoliquirilin, and additional recent flavonoid compounds such as glucoliquiritin apioside, phenyllicoflavoneA, shinflavanone, shinpterocarpin, and 1-methoxyphaseolin[16]. Volatile substances like hexanol, linalool oxide A and B, tetramethyl pyrazine, terpine-4-ol, geraniol, and different others may be isolated from the root. Glycyrrhizin, as well as glycyrrhetic acid, exist in 18 alpha and 18 beta stereoisomers. Glycyrrhizin may show different salt complexes as well as formed naturally as calcium and potassium salts. Carbenoxolone, a glycyrrhetic acid derivative, is used to prevent peptic ulcers [17,18].

Anti-inflammatory action

Glycyrrhiza glabra has anti-inflammatory properties that are achieved by blocking the pro-inflammatory factors listed below.

Action of glycyrrhetic acid and glycyrrhizin on COX-2 and TXA2

COX-2 is more prevalent in inflammatory disorders such as rheumatoid arthritis. CoX-2 activation transforms Arachidonic Acid (AA) into Prostaglandin H2 (PGH2). PGH2 is not stable and is transformed into PGE2, PGI, and TXA2 through the catalysis of Prostaglandin E Synthase (PGES), Prostacyclin Synthase (PGIS), and Thromboxane Synthase (TXAS)[19]. PGE2 has pro-inflammatory and immunosuppressive properties. PGI and TXA2 have mechanisms that contribute to the etiology of inflammatory disorders [20]. The COX-2 and TXA2 pathways are more important in the development of RA [21,22].

Glycyrrhiza glabra has anti-inflammatory effects and inhibits COX’s[23]. Glycyrrhetic acid inhibited the activity of many molecules, including COX-2, TXA’s, and NF-kB. GA inhibits the entire COX-2 and TXA2 pathway. In Figure 1 shows a pictorial representation of inhibition of inflammation-causing factor-like COX2, PGE2, TXA2. Glycyrrhetic acid and glycyrrhizin's major pharmacological target [21].It gives proof of anti-inflammatory and anti-tumor effects of GA and GL, as COX-2 and TXA-2 are the primary pathways for the development of RA [24,25].

pharmacy-pharmaceutical-inhibition

Figure 1: Flow diagram showing inhibition of inflammation causing factor like COX2, PGE2, TXA2.

Action of Glycyrrhiza glabra in p38/MAPK signaling pathway

The root of Glycyrrhiza glabra has many active substances such as flavonoid, saponin, glycyrrhetic acid, and other anti-inflammatory substances[26,27]. Glycyrrhiza glabra extract can operate in a variety of ways. It inhibits mitochondrial lipid peroxidation, phospholipase(A2), and reduces oxidative rate, reactive substance, and free radical production, all of which have pro-inflammatory effects. Glycyrrhiza glabra extract inhibits the lipopolysaccharide-induced inflammation and also aids in the suppression of NFkB and p38/MAPK signaling pathways, both of which are important for the activation of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) [28-30]. and also represent in Figures 2 and 3 respectively. Suppressing the p38/MAPK signaling pathway lowers cytokine production, inflammation, and protects against bone and cartilage loss [31].

pharmacy-pharmaceutical-glabra

Figure 2: Glycyrrhiza glabra extract action in pro-inflammatory mediators.

pharmacy-pharmaceutical-cytokines

Figure 3: Flow diagram for pro-inflammatory cytokines inhibition.

Inhibition of JAK-STAT signaling pathway

The JAK-STAT signaling pathway is the primary mechanism behind the causes of inflammation, such as in RA [32]. Tyrosine kinase, JAK-1, JAK-2, and JAK-3 are all linked with the Jak family cytokine receptor. Increased levels of pro-inflammatory cytokines like IL-1, IL-6, IL-17, and TNF-alpha can be detected. JAK-1 and JAK-2 activation lead to the phosphorylation of Signal Transducer and Activator of Transcription (STAT). The STAT dimer will translocate into the nucleus and bind to interferon-gamma at the target location [33]. The transcription of macrophages will cause the activation of cytokine resulting in synovial tissue damage [34]. The JAK-STAT signaling pathway because inflammation is inhibited by the glycyrrhiza glabra extract describe as a flow chart in Figure 4.

pharmacy-pharmaceutical-diagram

Figure 4: Flow diagram of JAK-STAT inhibition by Glycyrrhiza glabra.

Anti-diabetic activity

Diabetes is defined by a rise in blood glucose levels over time, commonly known as diabetes mellitus [35-37]. The major cause of a rise in blood glucose levels is a lack of glucose metabolism caused by faulty insulin production from pancreatic β-cell [38]. It will cause an increase in thirst, appetite, and urination [39,40]. Diabetes can lead to a variety of complications, including foot ulcers, stroke, heart failure, and kidney problems if left untreated for an extended length of time. Glycyrrhiza glabra root has a variety of medicinal properties [41,42]. Since it has anti-diabetic properties, Glycyrrhiza glabra can be used to treat diabetes on a long-term basis [43,44]. According to recent research, the Glycyrrhiza glabra ethanolic root contains phenolic compounds that are responsible for suppressing α-amylase as it aids in the hydrolysis of disaccharides, which aids in the management of diabetes [45].

Anti-viral activity

Glycyrrhiza contains antiviral properties that protect against virus fusion. It was discovered that Glycyrrhiza was most significant in limiting viral replication and may also be employed as a preventive measure. It has been utilized over the last year for patients who have been exposed to the Human immunodeficiency virus and chronic hepatitis virus [46,47]. According to much research, the root of Glycyrrhiza glabra was employed against the herpes simplex virus, fully deactivating the virus [48-50]. Glycyrrhiza glabra components such as Glycyrrhizic acid were utilized to deactivate herpes simplex virus particles [51]. Animal studies revealed that Glycyrrhiza glabra and its constituents help prevent herpes simplex virus encephalitis and lower the mortality rate [52]. Other studies suggest that Glycyrrhizic acid can assist to prevent the activation of many viruses in vitro [53,54]. Glycyrrhizin is also important in the prevention of several viral diseases like herpes simplex virus, poliovirus, SARS, Arboviruses, and flaviviruses [51,52,55-62].

Anti-cancer activity

The extract compounds of Glycyrrhiza glabra reduced the in-vivo and in-vitro proliferation of Ehrlich ascites tumor cells, as well as angiogenesis in-vitro, peritoneal, and chorioallantoic assays [63]. On the other sector, there is a wealth of evidence on the anticancer effects of its many constituents, both in-vivo and in-vitro study. Glycyrrhetic acid would trigger the proapoptotic cycle by altering mitochondrial permeability transition, which might be useful in promoting tumor cell death [64,65]. Glycyrrhiza alcoholic extract influences apoptosis and G1 cell cycle capture in MCF-7 human breast cancer cells [66].

When given at a dosage of 300 mg/kg, the Glycyrrhiza glabra extract isoliquiritigenin reduced the development of 1,2-dimethylhydrazine-induced colon and lung cancers in the case of mice [67]. The hydromethanolic extraction root of Glycyrrhiza glabra has antimutagenic activity and works by suppressing micronuclear production and chromosomal abnormality in albino mouse bone marrow [68,69].

Expectorant and antitussive activity

Glycyrrhiza glabra extract and powder are useful in avoiding infectious throat, cough, and bronchial catarrh. Because of glycyrrhizin, it has been showing antitussive, demulcent, and expectorant losing characteristics that aid in the relief of upper respiratory tract congestion and the acceleration of tracheal mucus secretion [70]. Liquiritin apioside, an active methanolic component of Glycyrrhiza glabra, aids in the suppression of capsaicin-induced cough [71]. It will relieve throat discomfort and have an expectorant effect. It stimulates bronchial mucus production and has demulcent and expectorant properties [72,73].

Antimicrobial activity

Glycyrrhiza glabra alcoholic root extract has antibacterial activity when tested against E coil, Pseudomonas fluorescence, B cereus, Enterococcus faecalis, and Staphylococcus aureus, with a maximum inhibition zone of 15 mm and the lowest inhibition zone of 22 mm [74]. Pseudomonas aeruginosa, S.typi, Vibrio mimicus, and Salminnella paratypi were evaluated against Glycyrrhiza glabra methalonic extract. Except for Pseudomonas aerugenosa, the methalonic extract demonstrated strong antibacterial activity against all experimental microorganisms. The strongest suppression is against Staphylococcus aureus, having a 22 mm inhibition zone [75]. Glycyrrhiza glabra extract, in combination with Glycrrhizic acid, inhibited the replication of various viruses, including hepatitis A, B, and C viruses along with Herpes simplex virus, Epstein-barr virus, Human immunodeficiency virus, SARS coronavirus, Influenza virus, Human cytomegalovirus, and varicella-zoster virus [76-87]. The coumarin extracts of Glycyrrhiza glabra, licopyranocoumarin, and Glycocoumarin, inhibit the development of large cells in HIV-infected cell culture. Licochalcone-A has anti-HIV properties [88,89]. Forty-two patients with haemophilia producing HIV-1 were treated with Glycyrrhiza extract for HIV management, and it was discovered that they improved in liver function, clinical function, and immunological function [90]. Glycyrrhizinic acid is used to treat pruritis, dermatitis, and cysts caused by parasite infection of the skin [91,92].

Anti- ulcer activity

According to clinical trials, carbaxolone, a Glycyrrhiza extract, has the most potent action against duodenal and stomach ulcers when taken a minimum dose of 100 mg thrice daily. Glycyrrhiza extract is beneficial for increasing the number of prostaglandins in the digestive system, which is beneficial for mucus secretion from the stomach and enhances the survival of higher cells in the stomach, as well as having anti-pepsin properties [93-97].

Hepatoprotective activity

Chronic hepatitis is a possible consequence of liver cirrhosis termed liver failure [98]. Glycyrrhiza glabra improves liver function and lowers serum aminotransferases when compared to a placebo. Prolonged usage of Glycyrrhiza glabra helps prevent hepatocellular cancer in chronic hepatitis C. According to in vitro research, Glycyrrhiza glabra developed intracellular transport and inhibited the surface antigen of the hepatitis B virus [99,100]. The formulation of 450 E1 can be reduced by Gycyrrhetic acid, Aglycone glycyrrhizin, and liver preservation [101]. Glycyrrhiza protects the oxidative and hepatic damage caused by flatoxin by arising the amount of CYP1A1 and Glutathione-S-transferase and also inhibits anticarcinogenic activity by rendering hepatoxin metabolic inactive [102]. In a mouse liver tissue investigation, the researchers discovered that hydromethanolic root components of Glycyrrhiza glabra protects against hepatotoxicity produced by carbon tetrachloride [103].

Discussion and Conclusion

Glycyrrhiza glabra is an old Ayurvedic medicinal plant that has been used in medicine. It has a variety of constituents, each with its unique therapeutic use. This plant's primary parts are the root, leaves, and rhizomes, which are utilized for medicinal purposes. The primary goal of the review is to demonstrate the various chemical components and pharmacological activity of Glycyrrhiza glabra with targeting various anti-inflammatory pathways like JACK-STAT, MAPK, COX2, and TXA-2 as well as anti-viral, anti-diabetic, expectorant and antitussive, anti-cancer, antimicrobial, anti-ulcer and hepatoprotective. To demonstrate the general mechanism of action with target specified enzyme or substrate to inhibit or overcome the unwanted action with the use of a natural agent of Glycyrrhiza glabra.

References

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