Potential of this drug is still unknown to its full extent , just few evaluations on this plant have been recorded & published, particularly in terms of its Ayurvedic value. Goal of this review was to look at Ayurvedic literature as well as current scientific information on Glycyrrhiza glabra to see whether there was any ancient- modern concordance.

Objectives

To evaluate the efficacy of Yashtimadhu in Urdhwajatru Vikaras through both ancient and modern science perspective.

Materials and Methods

Classical textbooks of ayurveda and other compilatory treatises are reviewed for documenting the information on Yashtimadhu. A thorough review of the published literature using online scientific search engines.

General description of Yashtimadhu

Yashtimadhu, scientifically known as Glycyrrhiza glabra Linn., belongs to the Fabaceae family. It is a perennial herbaceous plant that typically grows between 1 to 2 meters in height. The plant is characterized by a strong primary taproot about 15 cm long, which branches into 3 to 5 secondary roots, each extending up to 1.25 meters. It also produces several horizontal woody stolons, which can grow up to 8 meters in length. The plant generates new stems annually, which are sturdy, erect, and branched either from the base or higher up. These stems tend to be rough near the top. The leaves are alternate, pinnately compound, measuring 10 to 20 cm in length, and typically consist of 3 to 8 pairs of leaflets. The stipules are small and drooping. Yashtimadhu bears axillary inflorescences that are upright and spike-like, ranging from 10 to 15 cm long. The individual flowers are 1 to 1.5 cm in length, bluish to pale violet in color, and attached by short stalks. The calyx is short, bell-shaped, and covered with glandular hairs. Its fruit is a flat, erect pod measuring 1.5 to 2.5 cm in length and 4 to 6 mm in width, featuring thick sutures and a smooth, slightly netted surface. Each pod typically contains 3 to 5 brown, kidney-shaped seeds. Originally native to the Mediterranean region, Glycyrrhiza glabra is now widely cultivated in India, particularly in Punjab, Jammu & Kashmir, and parts of South India.^[8]

chalcone glucosides, 7-hydroxy-4′- methoxyiso-flavone (formetin), licuraside, liquiritoside, rhamno-liquiritin, triterpenoid, liquoric acid, 11-deoxo-glycyrrhetic acid, liquiritic acid, isoglabrolide, glab-rolide, deoxoglabrolide, glycyrrhizic acid, glycy-rrhetol, 21α- hydroxy- 11- deoxyglycyrrhetic, and 24- hydroxyglycyrrhetic acids, 18α-hydroxy glycyrrhetic acid, olean -12- en-3β-ol-30 oic, olean- 11, 13 (18)-dien-3β-ol-30 oic acid, glabranine (5,7- dioxy-8-3 (3′, 3′- dimethylallyl- flavanone), pino-cembrin, prunetin, 4- hydroxy chalcone, liqui-ritigenin, licoflavonol (6- γ-γ- dimethylallylkaemp-ferol), kumatakenin, glycerol, licoricone, glabridin, glabrol, liqurazid, liquiritin, 3-hydroxyglabrol, 4′-0- methyl glabridin, 3′- methoxyglabridin, glycyrrhetinic acid; methyl olean-11,13 (18)- diene-3, 24-diol-30-oate, glabranine, formononetin, glabrene, saponaretin (isovitexin), 24-hydroxy-11- deoxyglycyrrhetic acid, methyl olean 11, 13 (18) diene-3, glycerrhetol, 21α-hydroxy isoglabrolide, licoflavonol, glyzarin, glyzaglabrin, licoisoflavones A, B and licoisoflavon, glycyrin, sugars and aspargin (root and other plant parts).

Several bioactive compounds have been isolated from Glycyrrhiza glabra, including a water- soluble complex that constitutes approximately 40–50% of the plant’s total dry weight. This complex is made up of triterpene saponins, flavonoids, polysaccharides, pectins, simple sugars, amino acids, mineral salts, and various other constituents^[11] One of the primary components, glycyrrhizin—a triterpenoid compound—is responsible for the characteristic sweetness of licorice root. It exists as a mixture of potassium, calcium, and magnesium salts of glycyrrhizic acid, with concentrations typically ranging from 2% to 25%. Glycyrrhizic acid, one of the natural saponins, is a compound composed of a hydrophilic portion (two glucuronic acid molecules) and a hydrophobic segment (glycyrrhetic acid).^[12] The yellow coloration of licorice is attributed to its flavonoid content, particularly compounds like liquiritin, isoliquiritin (a chalcone), and others. Notably, isoflavones such as glabridin and hispaglabridins A and B exhibit strong antioxidant properties,^[13] while glabridin and glabrene also demonstrate estrogen-like activity.^[14]

These phytochemicals collectively contribute to the wide-ranging therapeutic properties of Yashtimadhu, reinforcing its importance in both traditional and modern medicinal systems.

Studies have shown that glycyrrhetic acid is 200 to 1,000 times more potent than glycyrrhizic acid in inhibiting 11-β-hydroxysteroid dehydrogenase, an enzyme involved in corticosteroid metabolism. Therefore, the pharmacokinetics of glycyrrhetic acid are of greater clinical relevance following oral intake. Once absorbed, glycyrrhetic acid is rapidly transported to the liver by carrier proteins, where it undergoes metabolism into glucuronide and sulfate conjugates. These conjugates are then hydrolyzed back into glycyrrhetic acid, which is reabsorbed into circulation, leading to delayed plasma clearance.^[23] In studies where healthy volunteers were given 100 mg of glycyrrhizin orally, glycyrrhetic acid was detected in plasma at levels below 200 ng/mL, while glycyrrhizin itself was not present. However, glycyrrhizin was detected in the urine within 24 hours, indicating that a portion of it may be absorbed intact.^[24]

Research studies on Glycyrrhiza glabra

Prevention of in-vitro glucose-induced cataract by Vasanjana prepared by Yashtimadhu Kalka (paste of Glycyrrhiza glabra Linn)^[25]

A study was conducted to evaluate the anti-cataract activity of Vasanjana, a formulation prepared using Yashtimadhu Kalka in the fat of domestic fowl, on glucose-induced cataract in sheep lenses. Cataract was induced by incubating sheep eye lenses in artificial aqueous humor containing 55 mM glucose.

Treatments included cow ghee (CG), plain fat, Vasanjana, and Vitamin E, all administered in the same medium. The lenses were incubated at room temperature for 72 hours.

Biochemical parameters analyzed included total protein content, malondialdehyde (MDA) levels, Na⁺/K⁺ ATPase activity, and electrolyte levels (Na⁺ and K⁺). Photographic documentation was also performed. Complete lens opacification was observed within 72 hours in the glucose-treated group.

These cataractous lenses exhibited a significant increase in Na⁺ and MDA levels, along with a significant reduction in total protein content and Na⁺/K⁺ ATPase activity. Lenses treated with Vasanjana showed a non-significant increase in total protein content, a decrease in MDA levels, and prevention of cataract formation and progression, as confirmed through photographic evidence.

From Cow ghee group - lens treated with high concentrated glucose and cow ghee

From Vasaanjana group (Vk) - lens treated with high concentrated glucose and Vasaanjana prepared by Yashtimadhu Kalka

Inhibitory Effects of Glycyrrhiza glabra and Its Major Constituent Glycyrrhizin on Inflamm-ation - Associated Corneal Neovasculari-zation^[26]

Glycyrrhizin, a key bioactive compound of Glycyrrhiza glabra, is known for its anti- inflammatory properties. This study aimed to evaluate the efficacy of Glycyrrhiza glabra methanolic extract and glycyrrhizin in the treatment of corneal neovascularization (CNV). The extract was prepared using 70% aqueous methanol and analyzed for its phytochemical composition through standard phytochemical tests, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC).

Topical formulations were prepared using Glycyrrhiza glabra methanol extract (2% w/v) and glycyrrhizin (1% w/v) in normal saline. CNV was induced in experimental animals through corneal alkali burns using 1 N NaOH. After allowing one week for neovascularization to develop, treatments commenced on day 7 and continued for 21 consecutive days. Each group received three drops of the respective topical solution three times daily. Phytochemical screening of the methanolic extract revealed the presence of saponins, phenols, carbohydrates, flavonoids, and proteins, while TLC and HPLC confirmed the presence of glycyrrhizin. Digital photographic analysis demonstrated a significant reduction in CNV in the extract- and glycyrrhizin-treated groups.

However, collagen fibers appeared disorganized and partially degraded. These findings suggest that while both Glycyrrhiza glabra extract and glycyrrhizin exhibit anti- CNV effects, the whole extract appears to be more effective in restoring normal corneal structure than glycyrrhizin alone.

Preventive Effect of Glycyrrhiza Glabra Extract on Oral Mucositis in Patients Under Head and Neck Radiotherapy: A Randomized Clinical Trial^[27]

Approximately two-thirds of cancer patients undergo radiotherapy, with oral mucositis being a common and serious side effect. It significantly contributes to patient morbidity, potential mortality, and a reduced quality of life. This study was conducted to evaluate the preventive effect of Glycyrrhiza aqueous extract on oral mucositis in patients receiving head and neck radiotherapy.

In this double-blind clinical trial, 37 patients with head and neck cancer were randomly assigned to two groups: an intervention group (n=19) receiving Glycyrrhiza aqueous extract, and a control group (n=18) receiving a placebo. Patients in the intervention group applied the extract topically twice daily, beginning on the first day of radiotherapy and continuing through the end of the second week. Prior to treatment, all participants were examined to rule out any pre-existing oral ulcers; those with existing oral wounds were excluded from the study.

The findings indicated that the use of Glycyrrhiza aqueous extract led to a reduction in the severity of oral mucositis, as well as decreased wound size and irritation. These results suggest that Glycyrrhiza root extract may be beneficial in preventing or alleviating oral mucositis and its associated complications in cancer patients undergoing radiotherapy.

Hair Growth Promotant Activity of Petroleum Ether Root Extract of Glycyrrhiza Glabra L (Fabaceae) in Female Rats^[28]

Female Wistar rats were used for the hair growth promotion studies. They were divided into three groups(n = 6) and their dorsal skin was completely denuded to completely remove hair. Paraffin oil (control), 2 % minoxidil solution (reference) or petroleum ether (60–80°C) root extract of Glycyrrhiza glabra (2 %), was applied to the denuded skin once daily for 30 days.

Ayurvedic texts recommend chewing Yastimadhu sticks - approximately nine inches in length - daily to help prevent dental caries and promote oral hygiene. Modern studies support these traditional practices by identifying several active phytochemicals in Yastimadhu, such as glycyrrhizol A, glycyrrhizol B, 5-O- methylglycryol, isoglycyrol, 6,8-diisoprenyl-5,7,4’-trihydroxyisoflavone, and gancaonin G. These compounds have demonstrated antimicrobial activity^[32] against cariogenic bacteria, including members of the Mutans group of Streptococci, Streptococcus sanguis, Lactobacillus spp., and Actinomyces spp. - all known contributors to dental caries.^[33]

In an animal study, MAIDS mice (infected with the LP-BM5 murine leukemia virus) were found to be 100 times more susceptible to Candida albicans infection than healthy mice. Treatment with glycyrrhizin significantly improved their resistance to the infection.^[34] Supporting this, an in vitro study by Motsei et al. revealed that licorice extracts, particularly from freshwater sources, had antifungal effects against C. albicans.^[35] Further research by Lee et al. identified that liquiritigenin (LG), a flavonoid in licorice, helped protect mice from systemic candidiasis by stimulating the CD4+ Th1 immune response.^[36]

Additionally, polysaccharides extracted from Glycyrrhiza glabra have been shown to possess strong anti-adhesive properties against Porphyromonas gingivalis, a major pathogen in periodontal disease.^[37]

Clinical studies on over-the-counter products like Canker Melts GX patches, which contain licorice extract, have shown that they reduce lesion size, duration, & discomfort in aphthous ulcers, thereby accelerating healing.^[38] In randomized, double- blind clinical trial involving 23 patients, dissolving oral patch containing licorice extract demonstrated superior results in reducing ulcer size & pain comp-ared to placebo, when used for up to eight days.^[39] These findings collecti. highlight therapeutic potential of Yastimadhu in maintaining oral health & managing various oral infections & conditions.

Discussion

Yashtimadhu (Glycyrrhiza glabra) widely recognized in Ayurveda, holds great therapeutic potential in the management of diseases above the clavicle,

The chemical composition of Glycyrrhiza glabra has been extensively explored in recent decades, which aided information of its bioactive constituents.

These compounds hold significant potential for yielding novel molecules with valuable therapeutic applications, making Glycyrrhiza glabra a promising source in the ongoing drug discovery and development process both classical Ayurvedic use and contemporary scientific studies support its therapeutic efficacy.

With further standardization and clinical validation, Yashtimadhu holds significant potential for integrative management of head and neck disorders.

References