Glabridin from Yashtimadhu-Licorice (Glycyrrhiza glabra)

Glabridin from Yashtimadhu-Licorice (Glycyrrhiza glabra)
Dr. Hemant Vinze M. S.
Glabridin displays pleotropic pharmacological activities. It is a key phytochemical found in Yashtimadhu-Licorice (Glycyrrhiza glabra). It can be said that all pharmacological activities of Yashtimadhu are due glabridin. In this article I discuss in detail the pharmacology of glabridin.


Molecular formula: C20H20O4
Structural formula:

Glabridin is an isoflavone, a type of isoflonoid found in the roots of yashtimadhu-licorice (Glycyrrhiza glabra). It is a yellowish-brown powder, insoluble in water but soluble in organic solvents such as propylene glycol. It is a hydrophobic chemical. Glabridin improves the functions of mitochondria. Glabridin stimulates DNA synthesis in human endothelial cells. Glabridin has bi-phasic effect on proliferation of human vascular smooth muscle. It is a natural skin lightener having no longterm side effects. In summary glabridin shows pleotropic pharmacological activity. I describe pharmacology of glabridin in detail below---- [1], [2], [3], [4]


Studies on five healthy male subjects showed that on oral administration, glabridin was well absorbed in the intestine, and its maximum concentration in blood reached in four hours and then eliminated relatively slowly in approximately ten hours at all doses. The multiple-dose studies with healthy male and female subjects for one week and four weeks suggested that plasma glabridin reached steady state levels within two weeks with a daily single dose administration of 300 to 1200 mg. No adverse effects were recorded even after repeated administration for four weeks. [5] 

In a study on rats it was found that the systemic bioavailability of glabridin was 7.5%, but increases when combined   with verapamil. The Caco-2 cell line is a continuous cell of heterogeneous human colorectal adenocarcinoma cells, developed by Sloan-Kettering Institute for Cancer Research. Incubation of verapamil significantly altered the intracellular accumulation of glabridin in Caco-2 cells. [6]

Actions of Glabridin in septic shock

Sepsis or septic shock is a life threatening emergency. In a study on animal models, anti-inflammatory, antioxidant, antimicrobial and cardio-respiratory-protective activities of glabridin were found to delay/avert death of animals with sepsis/septic shock. This suggests a possible application of glabridin for the management of sepsis/septic shock. [7]             

Anti-inflammatory/Antioxidant activity

Glabridin has anti-inflammatory, antioxidant and free radical scavenging, skin-whitening, neuroprotective, anti- atherogenic, estrogenic and anti-osteoporotic properties. Glabridin regulates food, dietary and energy metabolism. The biological activity of glabridin results from its capacity to down-regulate intra-cellular reactive oxygen species, bind to antioxidant effectors and act on estrogen receptors and act as plant based Selective Estrogen Receptor Modular (phyto SERM) [8]

Glabridin exhibits anti-inflammatory property through the inhibition of PGE (2), TXB (2) (COX), and LTB (4) [9]

Immunomodulatory activity

Dietary flavonoids like glabridin show anti-inflammatory and immunomodulatory activities. [10]

Antibacterial activity of glabridin

Since 1980 antibacterial activity of yashtimadhu-licorice (Glycyrrhiza glabra), especially its phytochemical glabridin has been well documented by many researchers. (Mitscher et al, 1980,  Demizu et al 1988, Okada et al, 1989, Haraguchi et al, 1998, Fukai et al 2002). Glabridin is active against Staphylococcus aureus, methicillin resistant    Staphylococcus aureus,  Staphylococcus epidermidis, Streptococcus mutans, Helicobacter pylori, Bacillus subtilis,   Enterococcus faecalis, Klebsiella pneumoniae, Salmonella typhi, Yersinia   enterocolitica, Enterobacter aerogens and Escherichia coli.                   

Vivek K Gupta et al had special interest in investigating antimicrobial potential of yashtimadhu-licorice (Glycyrrhiza glabra) against Mycobacterium tuberculosis. They found, at a concentration of 500g/mL, the extract of roots of yashtimadhu-licorice (Glycyrrhiza glabra) against Mycobacterium tuberculosis. The phytochemical identified to show this activity was glabridin. The antitubercular activity of glabridin was 20 times higher than that of crude extract. Through BACTEC assay the antimycobacterial  activity was tested against Mycobacterium tuberculosis H37Ra and    H37RV. The ethyl acetate extract of the plant showed antimycobacterial activity at a concentration range of 100-250 g/mL. The column fraction eluted with chloroform:ethyl acetate (96:4) was found to be more effective against tubercular bacilli at a concentration range of 50-120 g/mL. The antitubercular activity of glabridin was found to be good at a concentration of 29.16 g/mL against both the strains. [11]       

In an in vitro study, glabridin was tested for its antibacterial activity at concentrations ranging from 3.12 to 25 μg /mL against multi-drug-resistant Staphylococcus aureus. Glabridin displayed antibacterial activity  against multi- drug-resistant Staphylococcus aureus. This was attributed to antioxidant property of glabridin. Interestingly this activity was observed at a much lower concentration than expected. When combined with antibiotics such as oxacillin, norfloxacin, vancomycin etc. glabridin reduced the minimum inhibitory concentrations (MIC) of these antibiotics by up to     four-fold, while the minimum inhibitory concentration (MIC) of glabridin itself was found to be reduced by up to eight- fold. Thus glabridin is suitable for combination antibacterial therapy. [12]

Antiviral activity

Yashtimadhu-licorice (Glycyrrhiza glabra) contains more than 20 triterpenoids and 300 flavonoids. Of these very few show antiviral activity. Glabridin is an important antiviral agent. It shows antiviral activity against following viruses--------
Cerebral capillary vessel endothelial virus, coxsackie virus A 16, coxsackie virus B3, dehydroglyasperin C, duck hepatitis virus, enterovirus 17, hepatitis B virus, nepatitis C virus, human immunodeficiency virus, high-mobility-group box 1, human respiratory syncytial virus, herpes simplex virus, herpes simplex virus type 1, varicella (chicken pox) virus and varicella-zoster (shingles) virus.

The mechanism of antiviral activity of glabridin can be summarized as------- 
It affects release step while viral particles are infecting cells
It inhibits core gene expression of viruses  
It blocks the degradation of nuclear factor κB inhibitor IκB
It activates T lymphocyte proliferation
It suppresses virus-induced apoptosis
It prevents viral attachment to cells and stimulates interferon secretion
It reduces binding of virus to DNA and inhibits virus-polymerase activity
It reduces the levels of viral proteins at a step subsequent to virus entry. [13], [14]
Antifungal activity

Glabridin was found to be active against both yeast and fungi. At concentrations of 31.25 to 250 microgram/mL glabridin is active against Candida albicans and drug resistant mutant strains of fungi. [15]

The phytochemicals glabridin and licochalcone A found in yashtimadhu-licorice (Glycyrrhiza glabra) inhibit the growth of oral Candida albicans infection. They are very potent anti-fungal agents. They also work in synergy with nystatin. The phytochemical glycyrrhizic acid found in yashtimadhu-licorice (Glycyrrhiza glabra) has no anti-fungal effect. [16]

Antiparasitic activity

By inducing oxidative stress in Plasmodium falciparum parasite, glabridin inhibits in vitro, the growth of malarial parasite. Glabridin could induce apoptosis in Plasmodium falciparum. In erythrocytic cycle, trophozoit stage of Plasmodium falciparum  was found to be most sensitive to glabridin. These results suggest that glabridin can be a   cheap anti-malarial drug for tomorrow. [17]

Actions on the skin

In humans the enzyme tyrosinase is essential for the production of melanin, the pigment that imparts color to skin and eyes. The inflammatory reactions are induced in the skin when it is exposed to ultraviolet rays in the sunlight. Glabridin inhibits tyrosinase activity in cultured B 16 murine melanoma cells and guinea pig skin. It has no detectable effect on their DNA synthesis. Glabridin decreases the activities of T1 and T3 tyrosinase isozymes. Thus glabridin inhibits the production of melanin in the skin. Glabridin also inhibits UV-B induced erythema and skin pigmentation in guinea pig skins. The synthetic derivatives of glabridin also show similar activities. [18], [19]

Glabridin is poorly soluble in water. This impedes its topical application in cosmetic products. To overcome this difficulty, by using anti-solvent precipitation-homogenization method, a nanosuspension formulation of glabridin formulation has been developed. This improves the skin permeation of glabridin. 
The optimum formulation consisted of: 

Glabridin                                    0.25 %
Poloxamer 188                           0.47 %                         
Polyvinylpyrolidone K30           0.11 %

The obtained nanosuspension formulation showed an average particle size of 149.2 nm with a ploydispersity index of 0.254. The glabridin nanosuspension showed no significant particle aggregates and the drug loss after 3 months of storage at room temperature was 5.46%. With enhanced skin penetration, the nanosuspension might be a more preferable formulation for topical administration of poorly soluble glabridin. [20]

Ultra violet (UVB) radiation is the major etiological factor in the pathogenesis of aging and development of skin cancer. Glabridin and 18β-glycyrrhetinic acid, potent antioxidants from the extract of yashtimadhu-licirice (Glycyrrhiza glabra), protect the skin from UVB damage. They also prevent oxidative DNA fragmentation and the activation of proteins associated with apoptosis in human keratinocytes. [21]

Actions on wound healing

The anti-inflammatory property of glabridin reduces inflammation in wounds. At a low concentration of 1 x 10-8 mol/L, glabridin accelerates the formation of healthy granulation tissue and laying of fibroblasts; thus accelerating wound healing. [22]

Actions on the eye

Glabridin is a strong COX-2 inhibitor. Anti-inflammatory, antioxidant and free radical scavenging properties of glabridin alleviate retinopathy. [23]

Actions on musculoskeletal system

To investigate effects of glabridin on musculoskeletal system, glabridin was administered at 5, 10, 20 mg/kg body  weight for consecutive 28 days to BALB/c mice. Body mass, blood lactic acid (BLA), blood urea nitrogen (BUN), liver glycogen and muscle glycogen concentrations in mice were determined. The results showed that glabridin significantly increased exercise time, inhibited fatigue, delayed elevation of blood lactic acid and increased the storage of glycogen in the liver and muscles. Thus glabridin in yashtimadhu-licorice (Glycyrrhiza glabra) validates the tenet of Ayurveda:  "Yashtimadhu is a 'Rasaayana' drawya" [24] 

In vitro and in vivo glabridin and glabrene demonstrate actions similar to estradiol-17 β on osteoblasts, but differ in their extent of action and interactions with other drugs. Both glabridin and glabrene stimulated creatine kinase- specific activity in diaphysial bone and epiphysial cartilage of prepubertal female rats. However glabridin demonstrated superior activity in this regard. Pharmacological activity of glabridin also resembled to that of estradiol-17 β in ovariectomized female rats and in post-menopausal women. Glabrin has greater potential than glabrene, with or without   vitamin D, to modulate bone disorders in post-menopausal women. [25]   
The osteoblastic activity shows constructive bone forming activity. The osteoclastic activity destroys bone formation leading to osteoporosis. To evaluate the effect of glabridin, on osteoporosis, glabridin was administered to ovariectomized rats at a dose of 5 mg/kg body weight. The results obtained indicated that glabridin protected the animals from osteoprosis. The anti-osteoporosis activity of glabridin was attributed to estrogen-like activity of glabridin. Furthermore, glabridin was shown to inhibit osteoclastic activity and promote osteoblastic activity. However when administered at doses smaller than 5 mg/kg body weight, glabridin failed to show beneficial effects on the chemical composition and mechanical properties of bones in ovariectomized animals. [26], [27]   

By inhibiting receptor activator-induced osteoclast differentiation glabridin prevents osteoporosis. [28]

In another study on mice glabridin at a dose of 1-10 micro M significantly increased the function of osteoblastic cell line, caused a significant increase in alkaline phosphatase (ALP) activity, increase in collagen content and osteocalcin secretion in the cells. These effects were attributed to estrogen-like activity of glabridin. [29] 

Actions on the Breast

That glabridin shows estrogen like activity is now well established. The synthetic derivatives of glabridin also show similar properties. However glabridin was found to be three to four times more active than its derivatives 2'-O- methylglabridin and 4'-O-methylglabridin. Glbridin showed biphasic activity on breast-tumor-cells. At low       concentrations (10nM-10 microM) glabridin showed an estrogen receptor-dependent growth-promoting effect and at high concentrations (> 15 microM) glabridin demonstrated estrogen receptor-dependent anti-proliferative activity. [30]

In breast cancer, the cancer stem cells (CSCs) are thought to be the main cause for recurrence and metastasis. Therefore targeting CSCs is a new approach for the treatment of breast cancer. Glanridin is recently used for this purpose.  It is suggested that glabridin inhibits the cancer like properties of stem cells to arrest human breast cancer. [31] 

Some researchers suggested that glabridin displays its anti-breast cancer and anti-metastatic property through Fokal Anti Kinase (FAK)/Reactive Oxygen Species (ROS) pathway. The miRNA- family, which is frequently expressed at low levels in triple negative breast cancers, inhibits metastasis by blocking the epithelial-mesenchymal transition. In a study glabridin attenuated the migratory and invasive capacity of breast cancer cells by activating miR-200c. Glabridin induced the mesenchymal-epithelial transition in vitro and in vivo. Although many mechanisms for anti-breast cancer activities of glabridin are suggested, the exact mechanism of antitumor activity of glabridin at molecular level is still unclear. [32]

A study to evaluate effects of glabridin on adenocarcinoma of the breast showed that glabridin inhibits the proliferation of breast-cancer cells, by decreasing cell migration and invasion inhibits metastasis and decreases the angiogenesis of breast cancer. Glabridin also decreased the active forms of focal adhesion kinase. The study shows that, glabridin that acts in three ways: inhibition of migration, invasion and angiogenesis; may be a novel anticancer agent for the treatment of breast cancer. [33]

Actions on mouth

Chronic inflammation and persistent activation of myofibroblasts leads to oral submucous fibrosis. Oral submucous fibrosis (OSF) is a potentially malignant disorder. Betel nut (Areca nut) chewing is implicated in this pathological fibrosis. The chemical arecoline found in betel causes chronic inflammation and persistent activation of myofibroblasts. Glabridin prevents inflammation and inhibits activation of myofibroblasts. Thus glabridin is a natural anti-fibrosis compound for oral submucous fibrosis. [34]

Actions on CNS

Neuroprotective Effect

Stroke is a life-threarening disease characterized by focal or global disturbance of cerebral function. In a study on rats intraperitoneal injection of glabridin at a dose of 25 mg/kg body weight significantly decreased the volume of infarct. The clinical findings were supported by histological study of the infarcted area. Furthermore there was a significant elevation of levels of endogenous antioxidants i.e. superoxide dismutase (SOD) in the brain and reduction of glutathione. These findings suggest that glabridin has a neuroprotective effect against ischemia. [35]  

On learning and memory

Clinically glabridin at 1, 2 and 4 mg/kg body weight is used as nootropic agent. At higher doses (2 and 4 mg/kg body weight) glabridin significantly antagonizes the amnesia induced by 0.5 mg mg/kg body weight of scopolamine. Furthermore glabridin at doses 2 and 4 mg/kg body weight remarkably reduced the cholinesterase activity  in mice. Glabridin therefore appears to be a promising phytochemical in the management of Alzheimer's disease. [36]

Recently Chakravarthi and Avadhani have demonstrated anti-inflammatory, antioxidant activity. They also found a remarkable cholinesterase inhibitory activity of glabridin in the brain. Furthermore they found glabridin was useful to alleviate memory deficit. They attributed this effect to anti-inflammatory and antioxidant activities of glabridin. They think that glabridin can be useful in the management of Alzheimer's Disease (AD). [37] 

Beta-secretase 1 (BACE 1) also known as beta-site amyloid precursor protein cleaving enzyme 1. In humans it is encoded by BACE1 gene. It is important in the formation of myelin sheath. BACE 1 is required for the production of the neurotoxic β-amyloid peptide that is widely considered to have a crucial role in the etiology of Alzheimer's disease. [38]

Rui Yang Li et al found that higher doses of glabridin significantly antagonized amnesia induced by scopolamine. Glabridin also inhibits BACE 1. Rui et al therefore think that glabridin can be used in the management of Alzheimer's disease (AD) [39]

Antidepressant activity

The isoflavan glabridin and isoflavene glabrene found in yashtimadhu-licirice (Glycyrrhiza glabra) inhibit serotonin re-uptake thus showing antidepressant activity. They may be beneficial for mild to moderate depression in pre-menopausal and postmenopausal women. [40]

Effects on sleep

Licorice has been traditionally used for the treatment of insomnia. Glabridin in licorice potentiates GABA A and 5-HT (2C) receptors. This makes glabridin a useful anxiolytic, sedative and hypnotic agent. Glabridin has been recently recommended for the treatment of insomnia. Glabridin decreases the sleep latency and increases the duration of sleep. [41], [42], [43]
A study was designed to evaluate the effect of glabridin on isolated dorsal raphe neurons of rats. It was found that glabridin potentiated GABA (gamma amino butyric acid)-induced responses by positively modulating GABA-A. Thus glabridin displayed sedative and hypnotic effects comparable to diazepam. The activity was dose dependent. [44]  

Actions on CVS

Recently seven phytochemicals have been isolated from yashtimadhu-licorice (Glycyrrhiza glabra). 

(A) Isoflavans: (1) Hispaglabridin A (2) Hispaglabridin B (3) Glabridin (4) 4'-O-Methylglabridin 

(B) Chalcones: (5) Isoprenylchalcone derivatives (6) Isoliquitrigenin

(C) Isoflavone: Formononetin    
When tested for antioxidative capacities, flavans displayed the strongest capacity towards β-carotene and LDL, chalcones displayed moderate and isoflavone displayed the lowest capacity. Of isoflavans, glabrin displayed the strongest antioxidant activity towards LDL oxidation. As LDL oxidation is a key event in the formation of atherosclerotic lesion, glabridin may be useful in preventing or attenuating atherosclerosis. [45]

By preventing or attenuating the formation of atherosclerosis and by anti-inflammatory property, glabridin displays cardio-vascular protective effect. [46]
Lycopene, vitamin E, rosmarinic acid, carnosic acid, garlic and glabridin inhibit oxidation of LDL. However combination of lycopene, vitamin D, rosmarinic acid, carnosic acid, garlic and glabridin is a superior antioxidant than the individual chemical. [47]

In a study, pregnant female mice were fed on saturated fatty acids. Their adult mouse offspring, when exposed to high fat diet, developed hyperglycemia in their adult life, had lower levels of heart paraoxonase 2 (PON2), mRNA and protein                 expression. Glabridin prevented these ill effects of hyperglycemia. These effects in mice were verified in vitro. The results indicate that glabridin preserves the anti-atherogenic abilities of paraoxonase 2 (PON2). [48], [49]
Atherosclerosis preceded by chronic inflammation is a great scourge to cardiovascular diseases. Oxidation of low density lipoprotein (LDL) is the beginning of the end. In vitro and in vivo studies showed that glabridin and glabridin derivatives exhibit protective effect on cardiovascular system. The mechanisms of this protection can be summarized thus-----
1. They are strong anti-inflammatory agents
2. They prevent the oxidation of low density lipoprotein (LDL) and apolipoprotein E. They prevent the oxidation of LDL by inhibiting the formation of lipid peroxides and oxysterols.           
3. They prevent consumption of beta-carotene and lycopene (but do not protect vitamin E)
4. They prevent the activation of macrophages and dendritic cells.
5. They prevent the adhesion of molecules to endothelial cells.
They can be used as therapeutic agents for the treatment of cardiovascular diseases in future. [There are many research papers on cardiovascular-protective effects and anti-atherosclerotic effects of glabridin and glabridin derivatives. Here I have compiled them in short.] [50], [51], [52]

Pre-menopausal women being protected by estrogen are protected from cardio-vascular disease. Post menopausal women having lost estrogen protection have higher incidence of heart disease. Glabridin has estrogen-like activity. Glabridin protects post-menopausal women from the risk of cardio-vascular disease. Aberrant proliferation of vascular smooth muscle cells (VSMCs) promotes plaque formation. This leads to atherosclerosis. At high doses glabridin inhibits the proliferation of vascular smooth muscle cells (VSMCs) and arrests the formation of atherosclerosis. [53]

A group of researchers examined the effect of glabridin on mesenteric artery of rat using isometric myography. The results showed that glabridin induced vasorelaxation that was dependent on the opening of potassium (K+) channels. [54]
Delirium is a major, serious and dreadful complication of coronary artery bypass (CABG) surgery. This happens due to acute inflammation of the nervous system and reduced neurotransmitter serotonin. Neuroprotecctive activity of propofol can prevent delirium after CABG surgery. Recently anti-inflammatory, antioxidant and neuroprotective activity of glabridin has been shown to prevent post CABG delirium. Furthermore glabridin can also protect myocardium against ischemia-reperfusion injury. [55], [56], [57], [58]

Actions on RS

Yashtimadhu-licorice (Glycyrrhiza glabra) has been used as an antitussive and expectorant for centuries. Of many phytochemicals isolated from Yashtimadhu-licorice (Glycyrrhiza glabra) fourteen major compounds were evaluated on animal models for antitussive and expectorant activity. Glabridin was one of them. The results showed that most of them displayed strong antitussive and expectorant activity. Their antitussive effects depend on both peripheral and central mechanisms. [59]
Actions on GI system

Glabridin significantly increases gastric emptying time. Glabridin is a potent prokinetic agent comparable to domperidone. Glabridin relieves functional dyspepsia. [60]

Yashtimadhu-licorice (Glycyrrhiza glabra) has been used for acid peptic disease in India, China and Japan for centuries. Glabridin reduces gastric secretion and inhibits ulcer formation. Compounds such as glabridin, glycyrrhizin and aglycone  glycyrrhetinic acid protect the gastric mucosa from erosion by increasing secretion of mucus and by preventing the inflammation of gastric mucosa. This anti-ulcer activity is due to flavones contained in it. Glabridin is one of them. Recently flavones have been shown to inhibit the growth of Helicobacter pylori that is responsible for acid peptic disease. Furthermore flavonoids also inhibit the growth of Helicobacter pylori resistant to clarithromycin and amoxycillin. [61], [62]                                                                       
Acute colitis was induced in BALB/c mice by oral administration of 5 % dextran sodium sulphate (DDS) for seven days.  To evaluate the efficacy of glabridin for the treatment of inflammatory bowel disease, the animals were then treated with glabridin at doses 10 and 50 mg/kg body weight per day for seven days. Treatment with glabridin significantly attenuated mortality, loss of body weight and severity of clinical symptoms. Glabridin reduced the inflammation of the colon, improved the architecture and histology of the colon. Glabridin reduced the production of inflammatory mediators such as nitric oxide (NO), prostaglandin (PG) E2 and inflammatory cytokines. Thus glabridin may be useful for the treatment of inflammatory bowel disease. [63]

Actions on the liver


Flavonoids of yashtimadhu-licorice (Glycyrrhiza glabra) are reported to display hepatoprotective activity against CCl4 (Carbon tetrachloride) and acetaminophen. Glabridin is one such flavonoid. [64]

Viral hepatitis

For actions of glabridin on viral hepatitis see above.

Anti-hepatic tumor activity

A study showed that glabridin inhibited the proliferation of human hepatoma cells. Huh7 is a type of human liver cell that may be grown in the laboratory for research purposes. Depending upon dose glabridin induced apoptosis in Huh7 cells. Furthermore, autophagy was detected as early as 12 hours after exposure to low dose of glabridin. [65]    

In an experimental study glabridin significantly inhibited the migration/invasion capacities of hepatocellular carcinoma (HCC) cells. Furthermore administration of glabridin also effectively suppressed the tumor formation in the hepatoma xenograft model in vivo. Thus glabridin may have potential as a chemopreventive agent against hepatocellular carcinoma and liver cancer metastasis. [66]  

Actions on Pancreas

The ileum and pancreas display numerous morphological and functional changes in streptozotocin (STZ)-induced diabetes. A study on male albino rats showed that the treatment with glabridin significantly reduced the morphological and histological changes in the ileum and β cells of the pancreas. [67]

Actions on metabolism

A supercritical fluid (SCF) is any substance at a temperature and pressure above its critical point, where distinct liquid and gas phases do not exist. Supercritical fluids are suitable as a substitute for organic solvents in a range of industrial and laboratory processes. Carbon dioxide and water are the most commonly used supercritical fluids. [68]

To evaluate the anti-obesity effect of glabridin, mice were fed with high fat diet and glabridin-rich supercritical fluid extract of licorice. Glabridin showed inhibitory effect on adepogenesis in a dose-dependent manner. This effect resulted from binding protein alpha and peroxisome proliferator-activated receptor gamma. These studies suggest that glabridin and glabridin-rich licorice extract would be effective anti-obesity agent. [69]

Cytochrome P450 is the major drug metabolizing enzyme in humans. Glabridin inactivates the activities of cytochrome P450 by various mechanisms [70]  

A study was carried out on several rodents to evaluate the effect of glabridin on obesity. The results showed that glabridin decreased the weight of rodents and adiposity with concomitant reduction in the size of fat cells, ameliorated fatty liver and decreased the levels of cholesterol and triglyceride in blood. Glabridin suppressed the expression of lipogenic genes such as sterol regulatory binding transcription factor (SREBP)-1, fatty acid synthase (FAS), acetyl-Co-A carboxylase (ACC), stearoyl-Co A desaturase (SCD)-1 in white adipose tissue and liver. Glabridin also elevated the expression of fatty acid    oxidation genes such as carnitine palmitoyl transferase (CPT) 1, aceyl-CoA oxidase (ACO) and peroxisome proliferator- activated receptor (PPAR)-α in muscle. Moreover, glabridin enhanced phosphorylation of activated protein kinase (5'-AMP) or adenosine monophosphate-activated protein kinase (5' AMPK) in muscle and liver and promoted fatty acid xidation by modulating mitochondrial activity. This suggests that glabridin can be a novel molecule useful for the treatment of obesity. [71]

Actions in diabetes

In diabetic females, hyperglycemia abolishes cardiovascular and vascular protection offered by estrogen, leading to oxidative stress and inflammation. Administration of glabdrin abolished the oxidative stress induced by hyperglycemia, protected the cardiovascular and vascular system in diabetics under hyperglycemic state. This suggests that glabridin serves as an anti-inflammatory agent in diabetes related vascular dysfunction. [72]

In diabetic women the risk of death from cardiovascular disease is high. This is due to exacerbated oxidative stress. Even under high glucose stress the phytoestrogen glabridin displays antioxidant activity. It up-regulates the expression of manganese superoxide dismutase and prevents atherosclerosis in diabetic women. [73]   
Cognitive impairment occurs in diabetes mellitus. Glabridin at 5, 25 and 50 mg/kg body weight given orally (P.O.) to streptozotocin-induced diabetic rats, partially improved cognitive function. The dose of 5 mg/kg body weight did not improve cognitive function but higher doses i. e. 25 and 50 mg/kg body weight did. The combination of antioxidant, antidiabetic, neuroprotective and anticholinesterase properties of glabridin may be responsible for these effects. [74]
High glucose concentration in blood leads to glycosylation of amino groups of lysine residue in proteins. The glycosylation of proteins is an oxidation process. Addition of reducing agent not only prevents this process but also reverses it. The flavonoids found in plants show antioxidant properties. The plant flavonoids have long been used to prevent glycosylation. The flavonoid glabridin is a potent antioxidant. There is no much work on the use of glabridin for the prevention of glycosylation. In my opinion research should be carried out on the use of glabridin to prevent glycosylation.

Actions on Urinary System

Oral administration of glabridin at 30 mg/kg body weight per day for 10 days to mice suffering from glomerular nephritis significantly lowered ESR, reduced urinary excretion of protein and restored levels of serum creatinine and cholesterol to near normal. The anti-nephritic activity of glabridin was attributed to anti-inflammatory, antioxidant, radical scavenging and immunomodulatory properties of glabridin. [75] 

Actions on male reproductive system

Estrogen-like actions of glabridin are antagonistic to androgen. Glabrin may reduce male fertility. Glabridin can also be useful for the treatment of cancer of the prostate.

Actions of glabridin on female reproductive system

A study showed that glabridin was able to reduce the estrogenic response of E(2) by approximately 80 percent. Glabridin displayed ERα-selective antagonism, similar to the ERα-selective antagonist RU 58668. [76], [77]

Polycystic ovarian syndrome is characterized by anovulation, hyperandrogenism, hyperinsulinemia and insulin resistance. Young women with polycystic ovarian syndrome suffer from adverse coronary artery disease. A study on 32 women with polycystic ovarian syndrome treated with glabridin 10 μM daily for 12 months revealed a significant reduction in serum testosterone, fasting insulin and glucose. They displayed a significant reduction in insulin resistance and hirsutism. All women reverted to regular menstrual cycles. [78]

Ishikawa cell line is human endometrial adenocarcinoma cell line developed for cancer research. A study showed that the combination of 1 x 10 (-5) M tamoxifen and 1 x 10  (-6) M glabridin exhibited estrogenic activity and suppressed cell growth in Ishikawa cell line. This suggests that the combination therapy has potential to be used as estrogen

Antitumor activity

Peroxisome proliferator-activated receptor-γ (PPAR-γ or PPAR) is a type II nuclear receptor that in humans is encoded by the PPARG gene. PPARG is mainly present in adipose tissue, colon and macrophages. PPARG regulate glucose metabolism and fatty acid storage. Glabridin was shown to bind and activate PPAR-γ which inhibits the growth of cultured human breast, gastric, hepatic, lung, prostate and other cancer cells. [81], [82]             

Glabridin is a chemoprotective agent. It protects against neurotoxic side effects caused by doxorubicin. This protection is attributed to antioxidant activity of glabridin. [83]  



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18. Yokota et al, The inhibitory effect of glabridin from licorice extracts on melanogenesis  and inflammation, Pigment Cell Res.1998 Dec 11(6): 355-61      


20. Wang WP et al, Glabridin nanosuspension for enhanced skin penetration: formulation optimization, in vitro and in vivo evaluation, An International Journal of Pharmaceutical Sciences, Volume 71, Number 5, Publication date May 1, 2016. 

21. Veratti E et al, 18beta-glycyrrhetinic acid and glabridin prevent oxidative DNA fragmentation in UVB- irradiated human keratinocyte cultures, Anticancer Res. 2011 Jun; 31(6): 2209-15

22. Hong Yung Yip et al, The effects of glycyrrhizic acid and glabridin in regulation of CXCL5 inflammation gene on acceleration of wound healing, Asian Pacific Journal of Tropical Biomedicine, 10 Dec, 2015

23. Aruoma O. I. et al, Free Radicals, Antioxidants and Diabetes: Embryopathy, Retinopathy, Neuropathy and Cardiovascular Complications, Neuroembryology and Aging 2006-07; 4: 117-137             

24. Huaping Shang et al, Glabridin from Chinese Herb Licorice Inhibits Fatigue in Mice, African Journal of Traditional, Complimentary and Alternative Medicines 2010; 7(1): 17-23  
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27. Kaczmarczyk-Sedlak et al, Glabridin and glycyrrhizic acid show no beneficial effect on the chemical composition and mechanical properties of bones in ovariectomized rats, when administered in moderate dose, Pharmacol Rep. 2016 Oct; 68(5): 1036-40     

28. Kim HS, et al, Glabridin Inhibits Osteoclasts In Vitro, Int. J. Mol. Med, Feb 2012, 

29. Choi EM, The licorice root derived isoflavon glabridin increases the function of osteoblastic MC3T3-E1 Cells, Biochemical Pharmacology 01 August 2005, 70(3): 363-368

30. Tamir S et al, Estrogenic and antiproliferative properties of glabridin from licorice in human breast cells, Cancer Res. 2000 Oct 15; 60 (20): 5704- 9  

31. Jiang F et al, Glabridin inhibits cancer stem cell-like properties of human breast cancer cells: An epigenetic regulation of miR-148-a/SMAd2 signaling, Molecular Carcinog. 2016 May; 55(5): 829-40        

32. Ye X et al, Glabridin attenuates the migratory and invasive capacity of breast cancer cells by activating microRNA-200c, Cancer Sci 2014 Jul; 105 (7): 875-82 

33. Ya-Ling Hsu et al, Glabridin, an isoflavan from licorice root, inhibits migration, invasion, and angiogenesis of MDA-MB-231 human breast adenocarcinoma cells by inhibiting focal adhesion kinase/Rho signaling pathway, Molecular Nutrition & Food Research, 12 July 2010
34. Lee PH et al, Glabridin inhibits the activation of myofibroblasts in human fibrotic buccal fibroblasts through TGF-β/smad signaling, Environ Toxicol. 2017 Nov 9
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36. Cui YM et al, Effect of glabridin from Glycyrrhiza glabre on learning and memory in mice, Planta Med 2008 Mar; 74(4): 377-80                                 

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40. Rivka Ofir et al, Inhibition of Serotonin Re-uptake by Licorice Constituents, Journal of Molecular Neuroscience, May 2003, Volume 20, Issue 2, pp 135-140  

41. Zhenhua Jin et al, Potentiating Effect of Glabridin on GABA(A) Receptor Mediated Responses in Dorsal Raphe Neurones, Planta med 2013; 79: 1408-1412  

42. Cho SM et al, Hypnotic effects and binding studies for GABA (A) and 5-HT (2C) receptors of traditional medicinal plants used in Asia for insomnia, J Ethnopharmacol. 2010 Oct 28; 132(1): 225-32 

43. Katrin M. et al, Potentiating effect of glabridin from Glycyrrhiza glabra on GABA A receptors, Biochemistry and Biophysics Reports, Volume 6, July 2016, Pages 197-202 
44. Jin Z et al, Potentiating effect of glabridin on GABA A receptor-mediated responses in dorsal raphe neurons, Planta Med. 2013 Oct; 79 (15): 1408-12

45. Vaya J et al, Antioxidant constituents from licorice roots: isolation, structure elucidation and  antioxidative capacity towards LDL oxidatin, Free Radic Biol Med 1997; 23(2): 302-13

46. Kang MR et al, Cardiovascular protective effect of glabridin: Implications in LDL oxidation and inflammation, Int Immunopharmacol. 2015 Dec; 29 (2): 914-918
47. Fuhrman B et al, Lycopene synergistically inhibits LDL oxodation in combination with Vitamin E, glabridin, rosmarinic acid, carnosic acid or garlic, Antioxid Redox Signal 200Fall; 2(3):491-506

48. Yehuda I et al, Glabridin, an isoflavan from licorice root, upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation, Mol Nutr Food Res. 2016 Feb; 60 (2):287-99 

49. Yehuda I et al, Glabridin, a phytoestrogen from licorice root, up-regulates manganese superoxide dismutase, catalase and paraoxonase 2 under glucose stress, Phytother Res. 2011 May; 25(5): 659-67   

50. Kang MR et al, Cardiovascular protective effect of glabridin: Implications in LDL oxidation and inflammation, Int Immunopharmacol, 2015 Dec; 29(2): 914-918   

51. Carmeli E et al, The effect of an endogenous antioxidant glabridin on oxidized LDL, J Basic Clin Physiol Pharmacol 2008; 19(1): 49-63.

52. Belinky PA et al, The antioxidative effects of the isoflavan glabridin on endogenous constituents of LDL during its oxidation, Atherosclerosis 1998 Mar; 137 (1): 49-61; 

53. Somijen D et al, Estrogen-like activity of licorice root extracts: glabridin and glabrene, in vascular tissues in vitro and in vivo, J Steroid Biochem Mol Biol. 2004 Jul; 91(3): 147-55       

54. Chanda D et al, Glabridin-induced vasorelaxation: Evidence for a role of BKCa channels and cyclic GMP, Life Sci. 2016 Nov 15; 165: 26-34
55. Gorelick PB et al, Role of inflammation in cognitive impairment: results of observational epidemiological studies and clinical trials, Ann N Y Acad Sci. 2010; 1207: 155-162  

56. Murlidharan P et al, Cerebroprotective effect of Glycyrrhiza glabra Linn. root extract, Bangladesh Pharmacol 2008; 4: 60-64

57. Yu X-Q et al, In vitro and in vivo neuroprotective effect and mechanism of glabridin, a major active isoflavan from Glycyrrhiza glabra (G. glabra). Life Sci 2008; 68-78

58. Ojha S et al, Glycyrrhiza glabra protects from myocardial ischemia-reperfusion injury by improving emodynamic, biochemical, histopathological and ventricular function, Exp Toxicol Pathol 2013; 65: 219-227

59. Yi Kuang et al, Antitussive and expectorant activities of licorice and its major compounds, Bioorganic & Medicinal Chemistry, Available online 2 December 2017.   

60. Sasikumar Murugan et al, Effect of Flavonoid Rich Root Extract of Glycyrrhiza glabra on Gastric Emptying and Gastrointestinal Transit in Albino Wistar Rats, SOJ/ Pharmacy and Pharmaceutical Sciences/ Open Access, Published: April 24, 2017      

61. Toshio et al, Anti-Helicobacter pylori flavonoids from licorice extract, Life Sciences, Volume 17, Issue 12, 9 August 2002, Pages 1449-1463

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63. H-S Kwon et al, Glabridin, a functional compound of licorice, attenuates colonic inflammation in mice with dextran sulphate sodium-induced colitis, Clin. Exp Immunol. 2008 Jan; 15 (1): 165-173

64. Kuang Y et al, Screening of hepatoprotective compounds from licorice against carbon tetrachloride and acetaminophen induced Hep G2 cells injury, Phytomedicine, Volume 34, 15 October 2017, Pages 59-66     

65. Hsieh MJ et al, Glabridin induces apoptosis and autophagy through JNK 1/2 pathway in human hepatoma cells, Phytomedicine 2016 Apr 15; 23(4): 359-66 

66. Ming-Ju Hsieh et al, Glabridin inhibits migration and invasion by transcriptional inhibition of matrix metalloproteinsase 9 through modulation of NF-κB and AP-1 activity in human liver cancer cells, British Journal of Pharmacology, Volume 171, Issue 12, June 2014, Pages 3037-3050

67. Maha M et al, Effect of Glabridin on the Structure of Ileum and Pancreas in Diabetic Rats: A Histological, Immunohistochemical and Ultrastructural Study, Nature and Sceience, 2012; 10(3) 


69. Ahn J et al, Anti-obesity effect of glabridin-rich supercritical carbon dioxide extract of licorice in high-fat-fed obese mice, Food Chem Toxicol. 2013 Jan; 51:439-45  

70. Kent UM et al, The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9, Drug Metab Dispos. 2002 Jun; 30(6): 709-15        

71. Joo-Won Lee et al, AMPK activation with glabridin ameliorates adiposity and lipid dysregulation in obesity, J Lipid Res. 2012 July; 53(7): 1277-1286.  
72. Yehuda I et al, Glabridin, an isoflavan from licorice root, downregulates iNOS expression and activity under high-glucose stress and inflammation, Mol Nutr Food Res. 2015 Jun; 59(6):1041-52.  

73. Yehuda I et al, Glabridin, a phytoestrogen from licorice root, up-regulates manganese superoxide dismutase, a catalase and paraoxonase 2 under glucose stress, Phytother Res. 2011 May; 25 (5): 659-67
74. Hasanein P, Glabridin as a major active isoflavan from Glycyrrhiza glabra (licorice) reverses learning and memory deficits in diabetic rats, Acta Physiol Hung. 2011 Jan; 98(2): 221-30

75. Toshi T et al, Preliminary evaluation of antinephritic and radical scavenging activities of glabridin from Glycyrrhiza glabra, Fitoterapia, Volume 74, Issue 7-8, December 2003, Pages 624-629

76. Simons R et al, Agonistic and antagonistic estrogens in licorice root (Glycyrrhiza glabra), Anal Bioanal Chem. 2011 Jul; 401(1): 305-13

77. Boonmuen N et al, Licorice root components in dietary supplements are selective estrogen receptor modulators with a spectrum of estrogenic and anti-estrogenic activities, Steroids, 2016 Jan; 105: 42-49  

78. Bing-Guo Luan and Cai-Xia Sun, Effect of glabridin on insulin resistance, C-reactive protein and endothelial function in young women with polycystic ovary syndrome, Bangladesh Journal of Pharmacology 2015 Aug; Volume 10, No 3, 10: 681-687   

79. Jen SH et al, The combination effects of Glabridin and Tamoxifen on Ishikawa and MCF-7 Cell Lines, Nat Prod Commun, 2015 Sep; 10(9): 1573-6  

80. Su Wei Poh M et al, Estrogenicity of glabridin in Ishikawa cells, Plos one 2015 Mar 27, 10(3): e0121382 


82. Rebhun JF et al, Identification of glabridin as a bioactive compound in licorice (Glycyrrhiza glabra L) extract that activates human peroxisome proliferator-activated receptor gamma (PPAR- γ) Fitoterapia 2015 Oct; 106:55-61

83. Masoud Modarresia et al, Protective effects of glabridin  against cytotoxicity and oxidative stress induced by doxorubicin in PC 12 cells, Journal of Reports in Pharmaceutical Sciences, 2017, 6(1): 1-12 


alfachemistry said…
Our trained chemists work on custom projects designed specifically for the needs of each client. Glabridin

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