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Licorice is a natural product with unique properties containing licorice (Glycyrrhiza glabra) root.
The use of licorice dates back to ancient times. Its botanical name was derived from Greek words glukos – sweet and riza – root, because one of the active ingredients of licorice – glycyrrhizin is 50 times sweeter than sugar!
Licorice has been used in China for more than 5000 years. It was seen by many as an 'elixir of life', which increases vitality and energy level, slows the aging process.
The ancient Romans were so confident in licorice’s healing properties that they carried licorice with them on their moves. They also believed it increased personal stamina.
The main constituent found in licorice root is glycyrrhizin (glycyrrhizic acid); there are also other triterpenoid saponins, flavonoids and isoflavonoids, coumarins, resins, gums, tannin, sugar, starch and a bitter principle.
In recent years, many studies have confirmed the antiviral activity of glycyrrhizic acid. Flavonoids play an important role in the treatment of bacterial infection. Increasing antibiotic resistance has resulted in an urgent need for alternative therapies to treat diseases. Many studies have shown that licorice extracts have potent effects in inhibiting the activities of Gram-positive bacteria and Gram-negative bacteria, such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Bacillus subtilis. (1)
Licorice is most known for its soothing effect on inflamed mucous membranes of the throat, lungs, stomach and intestines. It has demulcent, soothing, anti-inflammatory, anti-spasmodic, and mild laxative properties. Licorice is adrenal cortex stimulant.
Glycyrrhizin increases the activity of ciliated epithelium, ease expectoration. Licorice has long been known for its ability to relieve respiratory ailments (such as bronchitis, colds, and sore throats) due to its anti-inflammatory and expectorate action.
Glycyrrhizin has anti-ulcer and anti-inflammatory action. It is traditionally used when mucous membranes of the digestive tract are inflamed or damaged. It produces highly viscous mucus over the stomach and duodenum walls, thus protecting them from irritation.
Evidence from human clinical trials indicates that licorice can alleviate gastritis and ulcers and is just as effective at healing of stomach ulcers as some medicaments. (2)
Licorice has a liver-protective effect. The mechanism of hepatoprotection includes inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. (3)
Clinical trials have demonstrated that glycyrrhizin, given intravenously as an isolated compound, can reduce elevated liver enzymes and reduce the risk of liver cancer in patients with active chronic hepatitis C. (4)
Current evidence suggests that licorice extract or certain compounds found in licorice including flavonoids, isoflavonoids, and triterpenes have beneficial effects in neurodegenerative diseases such as Alzheimer’s disease, and Parkinson’s disease. In addition, it has been shown that licorice extract can reduce neuroinflammatory processes after an acute ischemic damage to neural cells. (5)
Glycyrrhizin is effective against hyperglycemia, hyperlipidemia and associated oxidative stress, and may be a potential therapeutic agent for diabetes treatment. (6)
Glycyrrhiza may be appropriate as an adjunctive therapy for a variety of disorders involving mild adrenal insufficiency. Researchers have demonstrated the ability of licorice to treat adrenal insufficiency via enhancement of the adrenal cortisol response.
Licorice can be used to treat certain low blood pressure conditions. Because it can correct low potassium levels via effects on adrenal enzyme systems and support healthy adrenal function and aldosterone metabolism, Glycyrrhiza is primarily used to treat orthostatic hypotension. (10)
One of the important properties of licorice is its ability to enhance the effects of other herbs in the blend, to “harmonize” the ingredients. It is one of the reasons why licorice is used so widely in the folk medicine from the ancient times until now.
In in vitro combination experiments, glabridin was found to reduce the MIC of different antibiotics such as norfloxacin, oxacillin, and vancomycin by up to 4-fold.
A synergistic interaction was observed between norfloxacin and glabridin when used in combination against multidrug-resistant clinical isolate SA 4627 of Staphylococcus aureus at much lower concentrations, indicating the suitability of glabridin in combination therapy. (7)
It is important to use only the recommended dosage of licorice.
As a dietary supplement take 2 capsules with a large glass of water three times daily with meals.
Licorice is a common herb, which has been used, in traditional Chinese medicine for centuries. Presently we have summarized the antiviral and antimicrobial activities of licorice. Many studies found that several components were responsible for the antiviral and antimicrobial activities through different mechanisms. Licorice contains more than 20 triterpenoids and nearly 300 flavonoids. Among them, only two triterpenes, GL (glycyrrhizin) and GA (18β-glycyrrhetinic acid) have been reported to have antiviral effects. They can weaken virus activities by inhibiting virus gene expression and replication, reducing adhesion force and stress, and reducing HMGB1 binding to DNA. They can also enhance host cell activities by blocking the degradation of IκB, activating T lymphocyte proliferation and suppressing host cell apoptosis. GL is one of the major compounds isolated from the roots of licorice. In recent years, many studies have confirmed the antiviral activity of GL. Compared with GL, studies of the antiviral activity of GA are limited.
In contrast, flavonoids play an important role in the treatment of bacterial infection by decreasing expression of bacterial genes, inhibiting bacterial growth and reducing the production of bacterial toxin.
Increasing antibiotic resistance has resulted in an urgent need for alternative therapies to treat diseases. In recent years, many studies have shown that licorice extracts have potent effects in inhibiting the activities of Gram-positive bacteria and Gram-negative bacteria, such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Bacillus subtilis. (1)
One hundred patients with benign gastric ulceration were treated in a single-blind, endoscopically controlled trial to assess the relative efficacy of cimetidine (1 g daily) and Caved-S (six tablets daily).
Caved-S contains deglycyrrhizinated licorice.
Ulcer healing was assessed after six weeks' treatment, and, if incomplete, after a further six weeks. There was no significant difference between the two drug regimens (approximately 63% at six weeks and 91% at 12 weeks). If an ulcer remains unhealed after 10 weeks' treatment the patient should undergo surgery. There was no difference in the relief of day pain between the two drug regimens but cimetidine was more effective over the first two weeks of treatment relieving night pain, than was Caved-S (p less than 0 . 02). After ulcer healing, drug dosage was reduced (cimetidine to 400 mg at night and Caved-S to two tablets twice daily). So far, 56 patients, 28 in each group, have completed the first year's maintenance treatment, and there have been four ulcer recurrences in each group (14%). (2)
Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. (3)
In Japan, hepatitis C virus (HCV) is the single most frequent cause of hepatocellular carcinoma (HCC), resulting in yearly deaths of over 30,000. Although the mechanism of how HCV induces HCC is not clear, persistent HCV infection and necro-inflammatory changes in chronic hepatitis C accelerate the development of liver cirrhosis and can eventuate in HCC. Hence, means of eradicating HCV as well as suppressing inflammation in the liver, even if patients stay infected with HCV, would decrease the incidence of HCC with chronic hepatitis C. For more than 40 years, a preparation of glycyrrhizin [Stronger Neo-Minophagen C (SNMC)] has been used for the treatment of 'allergic' hepatitis in Japan. In 1977, intravenous injection with SNMC was started in patients with chronic hepatitis or liver cirrhosis, most of whom have turned out to be infected with hepatitis viruses. In a multicenter double-blind study, alanine aminotransferase (ALT) levels decreased in the patients who received 40 ml/day of SNMC for 4 weeks at a rate significantly higher (p < 0.001) than controls receiving placebo.
Furthermore, SNMC 100 ml/day for 8 weeks improved liver histology in 40 patients with chronic hepatitis, in correlation with improved ALT levels in serum.
Liver cirrhosis occurred less frequently in 178 patients on long-term SNMC than in 100 controls (28 vs. 40% at year 13, p < 0.002). Finally, HCC developed less frequently in the 84 patients on long-term SNMC than in the 109 controls (13 vs. 25% at year 15, p < 0.002). Combined, these results indicate that a long-term treatment with SNMC prevents the development of HCC in the patients with chronic hepatitis. SNMC is particularly helpful in the patients with chronic hepatitis C who fail to respond to interferon and in those who cannot be treated with it for various reasons. (4)
Licorice is a food and herbal medicine product from roots of Glycyrrhiza glabra plant. Medicinal use of licorice has been documented in ancient Greek and oriental civilizations. Recently, modern medical research studies have elaborated various medical properties of licorice root extract and its active ingredients. Many of these studies have investigated the effects of either licorice root extract or purified derivatives of this herbal plant on neurologic system in neural cultured tissues, animal models, and human studies. In the present study, existing literature regarding neurologic pharmacology of licorice was reviewed. Current evidence suggest that licorice extract or certain compounds found in licorice including flavonoids, isoflavonoids, and triterpenes have beneficial effects in neurodegenerative diseases such as Alzheimer’s disease, and Parkinson’s disease. In addition, it has been shown that licorice extract can reduce neuroinflammatory processes after an acute ischemic damage to neural cells. Licorice has been proven safe for human consumption in studied therapeutic dosages. These findings can lead to development and production of new drugs for neurodegenerative diseases. (5)
Glycyrrhizin is the main water-soluble constituent of the root of licorice (Glycyrrhiza glabra). The study investigates the effect of glycyrrhizin on streptozotocin (STZ)-induced diabetic changes and associated oxidative stress, including hemoglobin-induced free iron-mediated oxidative reactions.
Male Wistar rats were grouped as normal control, STZ-induced diabetic control, normal treated with glycyrrhizin, diabetic treated with glycyrrhizin and diabetic treated with a standard anti-hyperglycaemic drug, glibenclamide. Different parameters were studied in blood and tissue samples of the rats.
Glycyrrhizin treatment improved significantly the diabetogenic effects of STZ, namely enhanced blood glucose level, glucose intolerant behavior, decreased serum insulin level including pancreatic islet cell numbers, increased glycohemoglobin level and enhanced levels of cholesterol and triglyceride. The treatment significantly reduced diabetes-induced abnormalities of pancreas and kidney tissues. Oxidative stress parameters, namely, serum superoxide dismutase, catalase, malondialdehyde and fructosamine in diabetic rats were reverted to respective normal values after glycyrrhizin administration. Free iron in hemoglobin, iron-mediated free radical reactions and carbonyl formation in hemoglobin were pronounced in diabetes, and were counteracted by glycyrrhizin. Effects of glycyrrhizin and glibenclamide treatments appeared comparable.
Glycyrrhizin is effective against hyperglycemia, hyperlipidemia and associated oxidative stress, and may be a potential therapeutic agent for diabetes treatment. (6)
Glabridin a polyphenolic flavonoid from Glycyrrhiza glabra is known to possess several therapeutic properties. In the present study, we report for the first time the in vitro antibacterial activity (MIC values ranging from 3.12 to 25 μg/mL) of glabridin against multidrug-resistant clinical isolates of S. aureus by inducing oxidative stress. Increased levels of H2O2 and NO were observed in a dose-dependent manner after treatment of glabridin that further affected macromolecules such as DNA, lipids, and proteins. Surprisingly, glabridin was found to possess antioxidant properties when used at lower concentrations using three different methods including DPPH, FRAP, and SOD assays. In in vitro combination experiments, glabridin was found to reduce the MIC of different antibiotics such as norfloxacin, oxacillin, and vancomycin by up to 4-fold, while the MIC of glabridin itself was found to be reduced by up to 8-fold in the presence of antibiotics. A synergistic interaction was observed between norfloxacin and glabridin when used in combination against multidrug-resistant clinical isolate SA 4627 of Staphylococcus aureus at much lower concentrations, indicating the suitability of glabridin in combination therapy. (7)
Glycyrrhizic acid (GA), the major bioactive triterpene glycoside of glycyrrhiza, has been shown to possess a wide range of pharmacological properties, including anti-inflammatory and anti-viral properties. However, few studies have examined the anti-allergic activity and exact mechanism of action of GA. In the present work, the anti-allergic activity and possible mechanisms of action of GA on an immunoglobulin (Ig) E-mediated allergic reaction has been studied using three models of allergic reaction in vivo and in vitro. Active systemic allergic reaction in Balb/c mice showed that GA could suppress the increased level of IL-4 to restore the immune balance of TH1/TH2 cells in a dose-dependent manner. Additionally, GA attenuated significantly the B cells producing allergen-specific IgE and IgG1 partly because of the low levels of TH2 cytokines. Both passive cutaneous anaphylaxis in vivo and an RBL-2H3 cell-based immunological assay in vitro indicated that GA acted as a "mast cell stabilizer", as it inhibited mast cell degranulation and decreased vascular permeability by inhibiting the expression of Orai1, STIM1 and TRPC1, which blocked extracellular Ca2+ influxes. The current study suggests that GA may serve as an effective anti-allergic agent derived from food for the prevention and treatment of IgE-mediated allergic reaction. (8)
Excessive exposure to UV radiation negatively affects the human skin, characterized by photo-damage (premature aging & carcinogenesis). UV-B radiation causes about 90% of non-melanoma skin cancers by damaging de-oxy ribonucleic acids (DNA). In this study, we explored the effects & mechanisms of Glycyrrhizic acid (GA) against UV-B -induced photodamage using a well-established cellular model.
We used primary human dermal fibroblasts as a cellular model. The cells were cultured in the presence or absence of GA for 3,6, & 24 h. Effect of UV-B was assessed by examining cell viability, cell morphology, oxidative stress, ER stress, DNA damage & cellular autophagy levels through biochemical assays, microscopy & protein expression studies.
In this study, we have determined the effect of GA on autophagy mediated DNA damage response system as the main mechanism in preventing photodamage due to UV-B -irradiation to primary human dermal fibroblasts (HDFs). GA treatment to UV-B exposed HDFs, significantly inhibited cell death, oxidative & ER stress responses, prevented Cyclobutane Pyrimidine dimer (CPD) DNA adduct formation, and DNA fragmentation via modulation of UV-B induced autophagic flux. Present results showed that GA treatment quenched reactive oxygen species (ROS), relieved ER stress response, improved autophagy (6 hr's post-UV-B -irradiation) and prevented UV-B induced DNA damage.
The present study links autophagy induction by GA as the main mechanism in the prevention of DNA damage and provides a mechanistic basis for the photoprotective effect of GA and suggests that GA can be potentially developed as a promising agent against UV-B induced skin photo-damage. (9)
1. Liqiang Wang, Rui Yang, Bochuan Yuan, Ying Liu, and Chunsheng Liu. The antiviral and antimicrobial activities of licorice, a widely used Chinese herb. Acta Pharm Sin B. 2015 Jul; 5(4): 310–315. PMID: 26579460
2. Morgan AG, McAdam WAF, Pacsoo C, Darnborough A. Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy. Gut 1982; 23:545–51.
3. Jian-yuan Li, Hong-yan Cao, Ping Liu, Gen-hong Cheng, and Ming-yu Sun , Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review. Acta Pharm Sin B. 2015 Jul; 5(4): 310–315.
4. Kumada H. Long-term treatment of chronic hepatitis C with glycyrrhizin [stronger neo-minophagen C (SNMC)] for preventing liver cirrhosis and hepatocellular carcinoma. Oncology. 2002;62(suppl 1):94-100.
5. Parsa Ravanfar, Golnaz Namazi, Afshin Borhani-Haghighi, Shaghayegh Zafarmand. Neurologic Effects of Licorice: A Review. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
6. Sen S, Roy M, Chakraborti AS. Ameliorative effects of glycyrrhizin on streptozotocin-induced diabetes in rats. J Pharm Pharmacol. 2011 Feb;63(2):287-96. doi: 10.1111/j.2042-7158.2010.01217.x.
7. Singh V, Pal A, Darokar MP. A polyphenolic flavonoid glabridin: Oxidative stress response in multidrug-resistant Staphylococcus aureus. Free Radic Biol Med. 2015 Oct; 87:48-57. doi:10.1016/j.freeradbiomed.2015.06.016. Epub 2015 Jun 25.
8. Han S, Sun L, He F, Che H. Anti-allergic activity of glycyrrhizic acid on IgE-mediated allergic reaction by regulation of allergy-related immune cells. Sci Rep. 2017 Aug 3;7(1):7222.
9. Umar SA, Tanveer MA, Nazir LA, Divya G, Vishwakarma RA, Tasduq SA. Glycyrrhizic Acid Prevents Oxidative Stress Mediated DNA Damage Response through Modulation of Autophagy in Ultraviolet-B-Irradiated Human Primary Dermal Fibroblasts. Cell Physiol Biochem. 2019;53(1):242-257. doi: 10.33594/000000133.
10. Stansbury, Jill; Saunders, Paul; Winston, David; Zampieron, Eugene R. Treating Adrenal Insufficiency and Hypotension with Glycyrrhiza. Journal of Restorative Medicine, Volume 1, Number 1, 1 September 2012, pp. 102-106(5)