Unveiling Liquorice: A sweet journey through history, phytochemistry, and exceptional pharmacological activities

Document Type : Review Article

Authors

Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Egypt

Abstract

Radix Glycyrrhiza (liquorice), traditionally valued since old civilizations, continues to exhibit a wide range of beneficial properties across health, industry, and cosmetics. This sweet-tasting plant has been associated with numerous ancient cultures. It was used as a ritual beverage in ancient Egyptian tombs, described as the national treasure "Guo Lao" in Chinese medicine, and is featured in over 1250 Ayurvedic formulations under the Sanskrit name Yashtimadhu, meaning sweet stalk. Liquorice and its active compounds exhibit therapeutic potential across a wide spectrum of conditions, including those affecting the respiratory, digestive, nervous, cardiovascular, and immune systems. The broad spectrum of activities have been reported as antiviral, anticancer, anticoagulant, estrogenic, and many others. Recent research has also highlighted its applications in oral and eye diseases. Additionally, liquorice is extensively utilized in the cosmetics industry, with proven benefits for both skin and hair. This review provides a comprehensive overview of liquorice and its principal constituents, covering its historical significance, key phytochemicals, and diverse applications in the health and cosmetics fields as well. 
The safety profile of liquorice, along with potential risks associated with excessive consumption, is also addressed. Data for this review were sourced from scientific journals indexed in databases such as Web of Science, Springer, and Google Scholar, as well as pharmacopoeias and theses. This work aims to serve as a foundational reference for ongoing research into the therapeutic potential of liquorice modern medicine.

Highlights

•    Liquorice is one of the most well-known traditional herbal remedies worldwide.
•    Numerous chemical classes, such as triterpene saponins, flavonoids, and polysaccharides.
•    It is well-reputed for its antiviral, expectorant, and antiulcer activities.
•    Less known activities are anticoagulant, immunomodulating, and antidepressant.

Keywords

Main Subjects


(1)    Organization WH. WHO monographs on medicinal plants commonly used in the Newly Independent States (NIS): Libros Digitales-World Health Organization (WHO); 2010.
(2)    Wu SY, Wang WJ, Dou JH, Gong LK. Research progress on the protective effects of licorice-derived 18β-glycyrrhetinic acid against liver injury. Acta Pharmacol Sin. 2021;42(1):18-26.
(3)    Sharma V, Katiyar A, Agrawal RC. Glycyrrhiza glabra: Chemistry and Pharmacological Activity: Sweeteners. 2017 Jul 31:87-100. doi: 10.1007/978-3-319-27027-2_21. eCollection 2018.; 2017.
(4)    Öztürk M, Altay V, Hakeem KR, Akçiçek E.  Liquorice: From Botany to Phytochemistry. Cham: Springer International Publishing; 2017. p. 73-126.
(5)    Hayashi H, Sudo H. Economic importance of licorice. Plant Biotechnology. 2009;26(1):101-4.
(6)    Al-Snafi AE. Glycyrrhiza glabra: A phytochemical and pharmacological review. IOSR Journal of Pharmacy. 2018;8(6):1-17.
(7)    Hassan-Wassef H. Food habits of the Egyptians: newly emerging trends. East Mediterr Health J. 2004;10(6):898-915.
(8)    Quirós-Sauceda AE, Ovando-Martínez M, Velderrain-Rodríguez GR, González-Aguilar GA, Ayala-Zavala JF. Chapter 60 - Licorice (Glycyrrhiza glabra Linn.) Oils. In: Preedy VR, editor. Essential Oils in Food Preservation, Flavor and Safety. San Diego: Academic Press; 2015. p. 523-30.
(9)    Zhang Y, Yang Y, Gong H, Zhu H. A systematic review of the comparison of three medicinal licorices, based on differences of the types and contents about their bioactive components. Journal of Chemical Biology and Pharmaceutical Chemistry. 2018;1(1):1-6.
(10)    Nomura T, Fukai T. Phenolic Constituents of Licorice (Glycyrrhiza Species). In: Herz W, Kirby GW, Moore RE, Steglich W, Tamm C, editors. Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products. Vienna: Springer Vienna; 1998. p. 1-140.
(11)    Elgamal MH, Hady FK, Hanna AG, Mahran GH, Duddeck H. A further contribution to the triterpenoid constituents of Glycyrrhiza glabra L. Z Naturforsch C J Biosci. 1990;45(9-10):937-41.
(12)    Schmid C, Dawid C, Peters V, Hofmann T. Saponins from European Licorice Roots ( Glycyrrhiza glabra). J Nat Prod. 2018;81(8):1734-44.
(13)    Kuroda M, Mimaki Y, Honda S, Tanaka H, Yokota S, Mae T. Phenolics from Glycyrrhiza glabra roots and their PPAR-γ ligand-binding activity. Bioorganic & Medicinal Chemistry. 2010;18(2):962-70.
(14)    Zhou JX, Braun MS, Wetterauer P, Wetterauer B, Wink M. Antioxidant, Cytotoxic, and Antimicrobial Activities of Glycyrrhiza glabra L., Paeonia lactiflora Pall., and Eriobotrya japonica (Thunb.) Lindl. Extracts. Medicines (Basel). 2019;6(2).
(15)    Wei J-H, Zheng Y-F, Li C-Y, Tang Y-P, Peng G-P. Bioactive constituents of oleanane-type triterpene saponins from the roots of Glycyrrhiza glabra. Journal of Asian Natural Products Research. 2014;16(11):1044-53.
(16)    Hosseinzadeh H, Nassiri-Asl M. Pharmacological Effects of Glycyrrhiza spp. and Its Bioactive Constituents: Update and Review. Phytother Res. 2015;29(12):1868-86.
(17)    Dastagir G, Rizvi MA. Review - Glycyrrhiza glabra L. (Liquorice). Pak J Pharm Sci. 2016;29(5):1727-33.
(18)    Damle M. Glycyrrhiza glabra (Liquorice) - a potent medicinal herb. International Journal of Herbal Medicine. 2014;2(2 Part C):132-6.
(19)    Saxena S. Glycyrrhiza glabra: medicine over the millennium. Natural Product Radiance. 2005;4(5):358-67.
(20)    Wang L, Yang R, Yuan B, Liu Y, Liu C. The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharm Sin B. 2015;5(4):310-5.
(21)    Joseph J N, Shrivastava A, Benny B, Baig MY, Georgine S A, Saral A M. Antiviral properties of various bioactive components present in the root of Glycyrrhiza glabra. Current Nutrition & Food Science. 2023;19(2):166-75.
(22)    Huan C, Xu Y, Zhang W, Guo T, Pan H, Gao S. Research Progress on the Antiviral Activity of Glycyrrhizin and its Derivatives in Liquorice. Front Pharmacol. 2021;12:680674.
(23)    Wang J, Chen X, Wang W, Zhang Y, Yang Z, Jin Y, et al. Glycyrrhizic acid as the antiviral component of Glycyrrhiza uralensis Fisch. against coxsackievirus A16 and enterovirus 71 of hand foot and mouth disease. Journal of Ethnopharmacology. 2013;147(1):114-21.
(24)    Badam L. In vitro antiviral activity of indigenous glycyrrhizin, licorice and glycyrrhizic acid (Sigma) on Japanese encephalitis virus. J Commun Dis. 1997;29(2):91-9.
(25)    Soufy H, Yassein S, Ahmed AR, Khodier MH, Kutkat MA, Nasr SM, et al. Antiviral and immune stimulant activities of glycyrrhizin against duck hepatitis virus. African Journal of Traditional, Complementary and Alternative Medicines. 2012;9(3):389-95.
(26)    Mahrous RSR, Fathy H, Ibrahim RS. Metabolic bioprofiling of different Glycyrrhiza glabra solvent fractions for the identification of anti-adenoviral compounds using LC-HRMS/MS and in-vitro cytopathic assay coupled with chemometry. BMC Complementary Medicine and Therapies. 2023;23(1):259.
(27)    Fathy H, Abdelhady W, Ibrahim RS. In-silico Recognition of Liquorice Phytoconstituents Specially Glabranin B as a Potential Cathepsin L Inhibitor to Hinder 2019-NCOV Host Cell Entry. Int J Pharm Sci Rev Res. 2020;64.
(28)    Fu Y, Fang Y, Gong S, Xue T, Wang P, She L, et al. Deep learning-based network pharmacology for exploring the mechanism of licorice for the treatment of COVID-19. Scientific Reports. 2023;13(1):5844.
(29)    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.
(30)    Wu M, Wu Y, Deng B, Li J, Cao H, Qu Y, et al. Isoliquiritigenin decreases the incidence of colitis-associated colorectal cancer by modulating the intestinal microbiota. Oncotarget. 2016;7(51):85318-31.
(31)    Tang ZH, Li T, Tong YG, Chen XJ, Chen XP, Wang YT, et al. A Systematic Review of the Anticancer Properties of Compounds Isolated from Licorice (Gancao). Planta Med. 2015;81(18):1670-87.
(32)    Wang ZY, Nixon DW. Licorice and cancer. Nutr Cancer. 2001;39(1):1-11.
(33)    Wahab S, Annadurai S, Abullais SS, Das G, Ahmad W, Ahmad MF, et al. Glycyrrhiza glabra (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology. Plants (Basel). 2021;10(12).
(34)    Jain M, Yadav A, Tomar V, Kannojia P, Solanki S, Tonpay S. Possible pharmacological basis for antithrombotic effect of glycyrrhiza glabra in sprague dawley rats. Int J Pharm Sci Drug Res. 2009;1(2):113-5.
(35)    Mendes-Silva W, Assafim M, Ruta B, Monteiro RQ, Guimarães JA, Zingali RB. Antithrombotic effect of Glycyrrhizin, a plant-derived thrombin inhibitor. Thrombosis Research. 2003;112(1):93-8.
(36)    Jiang L, Wang Q, Shen S, Xiao T, Li Y. Discovery of glycyrrhetinic acid as an orally active, direct inhibitor of blood coagulation factor xa. Thrombosis Research. 2014;133(3):501-6.
(37)    Nakata N, Kira Y, Yabunaka Y, Takaoka K. Prevention of venous thrombosis by preoperative glycyrrhizin infusion in a rat model. Journal of Orthopaedic Science. 2008;13(5):456-62.
(38)    Ibrahim RS, Mahrous RSR, Abu El-Khair RM, Ross SA, Omar AA, Fathy HM. Biologically guided isolation and ADMET profile of new factor Xa inhibitors from Glycyrrhiza glabra roots using in vitro and in silico approaches. RSC Advances. 2021;11(17):9995-10001.
(39)    Shi C-C, Chen T-R, Zhang Q-H, Wei L-H, Huang C, Zhu Y-D, et al. Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies. RSC Advances. 2020;10(7):3626-35.
(40)    Shi CC, Chen TR, Zhang QH, Wei LH, Huang C, Zhu YD, et al. Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies. RSC Adv. 2020;10(7):3626-35.
(41)    Hajirahimkhan A, Simmler C, Yuan Y, Anderson JR, Chen SN, Nikolić D, et al. Evaluation of estrogenic activity of licorice species in comparison with hops used in botanicals for menopausal symptoms. PLoS One. 2013;8(7):e67947.
(42)    Tanaka T. A novel anti-dysmenorrhea therapy with cyclic administration of two Japanese herbal medicines. . Clin Exp Obstet Gynecol 2003:95-8.
(43)    Takeuchi T, Nishii O, Okamura T, Yaginuma T. Effect of traditional herbal medicine, shakuyaku-kanzo-to on total and free serum testosterone levels. Am J Chin Med. 1989;17(1-2):35-44.
(44)    Madak-Erdogan Z, Gong P, Zhao YC, Xu L, Wrobel KU, Hartman JA, et al. Dietary licorice root supplementation reduces diet-induced weight gain, lipid deposition, and hepatic steatosis in ovariectomized mice without stimulating reproductive tissues and mammary gland. Mol Nutr Food Res. 2016;60(2):369-80.
(45)    Lakshmi T, Geetha R. Glycyrrhiza glabra Linn. commonly known as licorice: a therapeutic review. Int J Pharm Pharm Sci. 2011;3(4):20-5.
(46)    Shamsi M, Nejati V, Najafi G, Pour SK. Protective effects of licorice extract on ovarian morphology, oocyte maturation, and embryo development in PCOS-induced mice: An experimental study. Int J Reprod Biomed. 2020;18(10):865-76.
(47)    Yang H, Kim HJ, Pyun BJ, Lee HW. Licorice ethanol extract improves symptoms of polycytic ovary syndrome in Letrozole-induced female rats. Integr Med Res. 2018;7(3):264-70.
(48)    Sabbadin C, Andrisani A, Zermiani M, Donà G, Bordin L, Ragazzi E, et al. Spironolactone and intermenstrual bleeding in polycystic ovary syndrome with normal BMI. J Endocrinol Invest. 2016;39(9):1015-21.
(49)    Yuan HN, Wang CY, Sze CW, Tong Y, Tan QR, Feng XJ, et al. A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia. J Clin Psychopharmacol. 2008;28(3):264-370.
(50)    Aoki F, Honda S, Kishida H, Kitano M, Arai N, Tanaka H, et al. Suppression by licorice flavonoids of abdominal fat accumulation and body weight gain in high-fat diet-induced obese C57BL/6J mice. Biosci Biotechnol Biochem. 2007;71(1):206-14.
(51)    Visavadiya NP, Narasimhacharya AV. Hypocholesterolaemic and antioxidant effects of Glycyrrhiza glabra (Linn) in rats. Mol Nutr Food Res. 2006;50(11):1080-6.
(52)    Armanini D, De Palo CB, Mattarello MJ, Spinella P, Zaccaria M, Ermolao A, et al. Effect of licorice on the reduction of body fat mass in healthy subjects. J Endocrinol Invest. 2003;26(7):646-50.
(53)    Fuhrman B, Volkova N, Kaplan M, Presser D, Attias J, Hayek T, et al. Antiatherosclerotic effects of licorice extract supplementation on hypercholesterolemic patients: increased resistance of LDL to atherogenic modifications, reduced plasma lipid levels, and decreased systolic blood pressure. Nutrition. 2002;18(3):268-73.
(54)    Kinoshita T, Maruyama K, Yamamoto N, Saito I. The effects of dietary licorice flavonoid oil supplementation on body balance control in healthy middle-aged and older Japanese women undergoing a physical exercise intervention: a randomized, double-blind, placebo-controlled trial. Aging Clin Exp Res. 2021;33(11):3099-108.
(55)    Upadhyay S, Ghosh AK, Singh V. Hair Growth Promotant Activity of Petroleum Ether Root Extract of Glycyrrhiza Glabra L (Fabaceae) in Female Rats. Tropical Journal of Pharmaceutical Research. 2013;11:753-8.
(56)    Saumendu DR, Raj KP, Suvakanta D, Jashabir C, Biswajit D. HAIR GROWTH STIMULATING EFFECT AND PHYTOCHEMICAL EVALUATION OF HYDRO-ALCOHOLIC EXTRACT OF GLYCYRRHIZA GLABRA. Global J Res Med Plants & Indigen Med| Volume. 2014;3(2):40-7.
(57)    Zhang B, Zhang W, Luo J, He J, Rong B, Zheng X, et al. Evaluation of hair growth properties of glycyrrhizic acid. Pharmacognosy Magazine. 2022;18(80).
(58)    Hagiwara K, Kiso A, Ono S, Kitamura H, Yamanishi H, Tsunekawa Y, et al. 18-β-Glycyrrhetinic Acid Promotes Hair Growth by Stimulating the Proliferation of Dermal Papilla Cells and Outer Root Sheath Cells, and Extends the Anagen Phase by Inhibiting 5α-Reductase. Biol Pharm Bull. 2024;47(7):1392-5.
(59)    Ruchi G, Rajiv S, Archana P, Yashu C, Neelesh. Review on antityrosinase activity of some Indian medicinal plants and. J Drug Deliv Ther. 2020:199-204.
(60)    Kang MH, Jang GY, Ji Y-J, Lee JH, Choi SJ, Hyun TK, et al. Antioxidant and Anti-Melanogenic Activities of Heat-Treated Licorice (Wongam, Glycyrrhiza glabra × G. uralensis) Extract. Current Issues in Molecular Biology. 2021;43(2):1171-87.
(61)    Zhu W, Gao J. Extracts as Topical Skin-Lightening Agents for the Improvement of Skin Pigmentation. J Investig Dermatol Symp Proc. 2008:20-4.
(62)    Amer M, Metwalli M. Topical liquiritin improves melasma. Int J Dermatol. 2000;39(4):299-301.
(63)    Ciganovic P, Jakimiuk K, Tomczyk M, Koncic MZ. Glycerolic licorice extracts as active cosmeceutical ingredients: Extraction. antioxidants. 2019:445.
(64)    Chakraborty A, Sahoo M, Roy SD, Dasgupta RK. Anti-ageing natural herbs: A systemic review. Indian Res J Pharm Sci. 2018:1589–98.
(65)    Cerulli A, Masullo M, Montoro P, Piacente S. Licorice (Glycyrrhiza glabra, G. uralensis, and G. inflata) and Their Constituents as Active Cosmeceutical Ingredients. Cosmetics. 2022;9(1):7.
(66)    Mees MA, Boone F, Bouwen T, Vanaerschot F, Titeca C, Vikkula HK, et al. Glycyrrhizin-Based Hydrogels Accelerate Wound Healing of Normoglycemic and Diabetic Mouse Skin. Pharmaceutics. 2022;15(1).
(67)    Tanideh N, Rokhsari P, Mehrabani D, Mohammadi Samani S, Sabet Sarvestani F, Ashraf MJ, et al. The Healing Effect of Licorice on Pseudomonas aeruginosa Infected Burn Wounds in Experimental Rat Model. World J Plast Surg. 2014;3(2):99-106.
(68)    Assar DH, Elhabashi N, Mokhbatly AA, Ragab AE, Elbialy ZI, Rizk SA, et al. Wound healing potential of licorice extract in rat model: Antioxidants, histopathological, immunohistochemical and gene expression evidences. Biomed Pharmacother. 2021;143:112151.
(69)    Zabihi M, Hatefi B, Ardakani ME, Ranjbar AM, Mohammadi F. Impact of licorice root on the burn healing process: A double-blinded randomized controlled clinical trial. Complement Ther Med. 2023;73:102941.
(70)    Ikegami N, Akatani K, Imai M, Yoshioka K, Yano S, editors. Prophylactic effect of long-term oral administration of glycyrrhizin on AIDS development of asymptomatic patients. Int Conf AIDS; 1993.
(71)    Isbrucker RA, Burdock GA. Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin. Regul Toxicol Pharmacol. 2006;46(3):167-92.
(72)    Utsunomiya T, Kobayashi M, Pollard RB, Suzuki F. Glycyrrhizin, an active component of licorice roots, reduces morbidity and mortality of mice infected with lethal doses of influenza virus. Antimicrob Agents Chemother. 1997;41(3):551-6.
(73)    Chandran A, Syam RJ, Jerone JJ, V SK. Ethnopharmacological study about Glycyrrhiza glabra L. (Licorice) based on Ayurveda, An Indian System of Traditional Medicine- A Review. International Journal of Ayurvedic Medicine. 2022;13(3):587-600.
(74)    Chakravarthi KK, Avadhani R. Beneficial effect of aqueous root extract of Glycyrrhiza glabra on learning and memory using different behavioral models: An experimental study. J Nat Sci Biol Med. 2013;4(2):420-5.
(75)    Dhingra D, Parle M, Kulkarni SK. Memory enhancing activity of Glycyrrhiza glabra in mice. Journal of Ethnopharmacology. 2004;91(2):361-5.
(76)    Sheshagiri S, Patel KS, Rajagopala S. Randomized placebo-controlled clinical study on enhancement of Medha (intelligence quotient) in school going children with Yahstimadhu granules. Ayu. 2015;36(1):56-62.
(77)    Petramfar P, Hajari F, Yousefi G, Azadi S, Hamedi A. Efficacy of oral administration of licorice as an adjunct therapy on improving the symptoms of patients with Parkinson's disease, A randomized double blinded clinical trial. J Ethnopharmacol. 2020;247:112226.
(78)    Rode MR, Kolhe SU, Patil CN. "Therapeutic potential of licorice extract in a prenatal valproic acid model of autism spectrum disorder in Wistar rats: Neurobehavioral and neurobiochemical insights". Brain Disorders. 2024;14:100128.
(79)    Guo J, Yang CX, Yang JJ, Yao Y. Glycyrrhizic Acid Ameliorates Cognitive Impairment in a Rat Model of Vascular Dementia Associated with Oxidative Damage and Inhibition of Voltage-Gated Sodium Channels. CNS Neurol Disord Drug Targets. 2016;15(8):1001-8.
(80)    Komatsu T, Ohta H, Motegi H, Hata J, Terawaki K, Koizumi M, et al. A novel model of ischemia in rats with middle cerebral artery occlusion using a microcatheter and zirconia ball under fluoroscopy. Sci Rep. 2021;11(1):12806.
(81)    Sarkar S, Shaw P, Singh P, Acharya Chowdhury A. Emerging neuroprotective potential of Liquorice: Mechanistic insights for neurological disorders. South African Journal of Botany. 2023;154:149-58.
(82)    Cui YM, Ao MZ, Li W, Yu LJ. Effect of glabridin from Glycyrrhiza glabra on learning and memory in mice. Planta Med. 2008;74(4):377-80.
(83)    Yang E-J, Min JS, Ku H-Y, Choi H-S, Park M-k, Kim MK, et al. Isoliquiritigenin isolated from Glycyrrhiza uralensis protects neuronal cells against glutamate-induced mitochondrial dysfunction. Biochemical and Biophysical Research Communications. 2012;421(4):658-64.
(84)    Elendu C. The evolution of ancient healing practices: From shamanism to Hippocratic medicine: A review. Medicine. 2024;103(28):e39005.
(85)    Dhingra D, Sharma A. Antidepressant-like activity of Glycyrrhiza glabra L. in mouse models of immobility tests. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2006;30(3):449-54.
(86)    Dhingra D, Sharma A. Evaluation of antidepressant-like activity of glycyrrhizin in mice. Indian Journal of Pharmacology. 2005;37:390-4.
(87)    Li HF. Study on the Main Efficacy and Mechanism of Antidepressant Effect of Liquiritin. Thesis, Beijing University of Chinese Medicine. 2008.
(88)    Wang R, Chen Y, Wang Z, Cao B, Du J, Deng T, et al. Antidepressant effect of licorice total flavonoids and liquiritin: A review. Heliyon. 2023;9(11):e22251.
(89)    Wang W, Hu X, Zhao Z, Liu P, Hu Y, Zhou J, et al. Antidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1179-84.
(90)    Mahrous RSR, Fathy HM, Ibrahim RS. Metabolic bioprofiling for discovering xanthine oxidase inhibitors from Glycyrrhiza glabra root solvent fractions using orthogonal separation modalities coupled with chemometry. South African Journal of Botany. 2023;154:251-9.
(91)    Aung KH, Liu H, Ke Z, Jiang S, Huang J. Glabridin Attenuates the Retinal Degeneration Induced by Sodium Iodate In Vitro and In Vivo. Front Pharmacol. 2020;11:566699.
(92)    Burillon C, Chiambaretta F, Pisella PJ. Efficacy and safety of glycyrrhizin 2.5% eye drops in the treatment of moderate dry eye disease: results from a prospective, open-label pilot study. Clin Ophthalmol. 2018;12:2629-36.
(93)    Jhanji V, Liu H, Law K, Lee VY, Huang SF, Pang CP, et al. Isoliquiritigenin from licorice root suppressed neovascularisation in experimental ocular angiogenesis models. Br J Ophthalmol. 2011;95(9):1309-15.
(94)    Sidhu P, Shankargouda S, Rath A, Hesarghatta Ramamurthy P, Fernandes B, Kumar Singh A. Therapeutic benefits of liquorice in dentistry. Journal of Ayurveda and Integrative Medicine. 2020;11(1):82-8.
(95)    AlDehlawi H, Jazzar A. The Power of Licorice (Radix glycyrrhizae) to Improve Oral Health: A Comprehensive Review of Its Pharmacological Properties and Clinical Implications. Healthcare (Basel). 2023;11(21).
(96)    Khan SF, Shetty B, Fazal I, Khan AM, Mir FM, Moothedath M, et al. Licorice as a herbal extract in periodontal therapy. Drug Target Insights. 2023;17:70-7.
(97)    He J, Chen L, Heber D, Shi W, Lu Q-Y. Antibacterial Compounds from Glycyrrhiza uralensis. Journal of Natural Products. 2006;69(1):121-4.
(98)    Liu G, He YH, Zhang FF, Kong XL, Wen YL, Ma QR, et al. [Effects of glycyrrhizic acid on the growth and acid-producing of Streptococcus mutans in vitro]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2010;41(4):634-7.
(99)    Hu CH, He J, Eckert R, Wu XY, Li LN, Tian Y, et al. Development and evaluation of a safe and effective sugar-free herbal lollipop that kills cavity-causing bacteria. Int J Oral Sci. 2011;3(1):13-20.
(100)    Mentes JC, Kang S, Spackman S, Bauer J. Can a licorice lollipop decrease cariogenic bacteria in nursing home residents? Res Gerontol Nurs. 2012;5(4):233-7.
(101)    Peters MC, Tallman JA, Braun TM, Jacobson JJ. Clinical reduction of S. mutans in pre-school children using a novel liquorice root extract lollipop: a pilot study. Eur Arch Paediatr Dent. 2010;11(6):274-8.
(102)    Feldman M, Grenier D. Cranberry proanthocyanidins act in synergy with licochalcone A to reduce Porphyromonas gingivalis growth and virulence properties, and to suppress cytokine secretion by macrophages. J Appl Microbiol. 2012;113(2):438-47.
(103)    Moghadamnia AA, Motallebnejad M, Khanian M. The efficacy of the bioadhesive patches containing licorice extract in the management of recurrent aphthous stomatitis. Phytother Res. 2009;23(2):246-50.
(104)    Badr AE, Omar N, Badria FA. A laboratory evaluation of the antibacterial and cytotoxic effect of Liquorice when used as root canal medicament. Int Endod J. 2011;44(1):51-8.
(105)    Ferrucci LM, Bell BP, Dhotre KB, Manos MM, Terrault NA, Zaman A, et al. Complementary and alternative medicine use in chronic liver disease patients. J Clin Gastroenterol. 2010;44(2):e40-5.
(106)    Lee CH, Park SW, Kim YS, Kang SS, Kim JA, Lee SH, et al. Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice. Biol Pharm Bull. 2007;30(10):1898-904.
(107)    Shibata S. A drug over the millennia: pharmacognosy, chemistry, and pharmacology of licorice. Yakugaku Zasshi. 2000;120(10):849-62.
(108)    Chen H-J, Kang S-P, Lee IJ, Lin Y-L. Glycyrrhetinic Acid Suppressed NF-κB Activation in TNF-α-Induced Hepatocytes. Journal of Agricultural and Food Chemistry. 2014;62(3):618-25.
(109)    Takii H, Kometani T, Nishimura T, Nakae T, Okada S, Fushiki T. Antidiabetic Effect of Glycyrrhizin in Genetically Diabetic KK-Ay Mice. Biological and Pharmaceutical Bulletin. 2001;24(5):484-7.
(110)    Zhang Y, Xu Y, Zhang L, Chen Y, Wu T, Liu R, et al. Licorice extract ameliorates hyperglycemia through reshaping gut microbiota structure and inhibiting TLR4/NF-κB signaling pathway in type 2 diabetic mice. Food Res Int. 2022;153:110945.
(111)    Murray MT. Glycyrrhiza glabra (Licorice): Textbook of Natural Medicine. 2020:641-647.e3. doi: 10.1016/B978-0-323-43044-9.00085-6. Epub 2020 Jul 10.; 2020.
(112)    El-Saber Batiha G, Magdy Beshbishy A, El-Mleeh A, Abdel-Daim MM, Prasad Devkota H. Traditional Uses, Bioactive Chemical Constituents, and Pharmacological and Toxicological Activities of Glycyrrhiza glabra L. (Fabaceae). Biomolecules. 2020;10(3).
(113)    Bozic DD, Milenkovic M, Ivkovic B, Cirkovic I. Newly-synthesized chalcones-inhibition of adherence and biofilm formation of methicillin-resistant Staphylococcus aureus. Braz J Microbiol. 2014;45(1):263-70.
(114)    Tsukiyama R, Katsura H, Tokuriki N, Kobayashi M. Antibacterial activity of licochalcone A against spore-forming bacteria. Antimicrob Agents Chemother. 2002;46(5):1226-30.
(115)    Lim TK. Glycyrrhiza glabra: Edible Medicinal and Non-Medicinal Plants. 2015 Oct 22:354-457. doi: 10.1007/978-94-017-7276-1_18.; 2015.
(116)    Kuang Y, Li B, Fan J, Qiao X, Ye M. Antitussive and expectorant activities of licorice and its major compounds. Bioorganic & Medicinal Chemistry. 2018;26(1):278-84.
(117)    Rao KV. A review on licorice. Anc Sci Life. 1993;13(1-2):57-88.
(118)    Deutch MR, Grimm D, Wehland M, Infanger M, Krüger M. Bioactive Candy: Effects of Licorice on the Cardiovascular System. Foods. 2019;8(10).
(119)    Kwon Y-J, Son D-H, Chung T-H, Lee Y-J. A Review of the Pharmacological Efficacy and Safety of Licorice Root from Corroborative Clinical Trial Findings. Journal of Medicinal Food. 2019;23(1):12-20.
(120)    Liu JF, Srivatsa A, Kaul V. Black licorice ingestion: Yet another confounding agent in patients with melena. World J Gastrointest Surg. 2010;2(1):30-1.
(121)    Edelman ER, Butala NM, Avery LL, Lundquist AL, Dighe AS. Case 30-2020: A 54-Year-Old Man with Sudden Cardiac Arrest. New England Journal of Medicine. 2020;383(13):1263-75.
(122)    Ceccuzzi G, Rapino A, Perna B, Costanzini A, Farinelli A, Fiorica I, et al. Liquorice Toxicity: A Comprehensive Narrative Review. Nutrients. 2023;15(18).
(123)    Sontia B, Mooney J, Gaudet L, Touyz RM. Pseudohyperaldosteronism, liquorice, and hypertension. J Clin Hypertens (Greenwich). 2008;10(2):153-7.