Evaluation of Glycyrrhiza Species as Medicinal Plant

Abstract

In this study, Glycyrrhiza species cultivated in Turkey assessed in terms of their chemical composition, morphological features and therapeutic activities. Potassium and calcium salts including licritic acid, gylcertatol and glycyrrhic acid have been found in the roots. Glycyrrhizin, a cough suppressor and natural antioxidant, has been determined as major triterpenoid saponin found in roots. Studies revealed that leaves contain flavonoids which have antioxidant and anti-inflammatory effect. Glycyrrhiza species have economic value due to their compounds with different bioactivities such as antioxidant, anti-inflammatory, antimicrobial activity. In recent studies, besides of known therapeutic effects of active compounds obtained from Glycyrrhiza species, it has been investigating whether they have a neuroprotective effect for Alzheimer's disease therapy. In the light of the data in the literature, it has also been revealed side effects of active compounds in this plant species. On the other hand, the side effects of active compounds isolated from these species have been manifested with various data. To find their new bioactive compounds against different diseases, studies on Glycyrrhiza species should be increased.

Keywords

• Glycyrrhiza
• Therapeutic Agent
• Phenolic Compounds
• Antiviral
• Antioxidant

References

1. [1] Armanini, D., et al., History of the endocrine effects of licorice. Experimental and clinical endocrinology & diabetes, 2002. 110(06): p. 257-261.
2. [2] KARAMAN, Ö. and G. ELGİN CEBE, Diyabet ve Türkiye’de antidiyabetik olarak kullanılan bitkiler. 2004.
3. [3] inflata Bat, G. and G. uralensis Fisch, Meyan.
4. [4] Fiore, C., et al., A history of the therapeutic use of liquorice in Europe. Journal of ethnopharmacology, 2005. 99(3): p. 317-324.
5. [5] Jatav, V.S., et al., Recent pharmacological trends of Glycyrrhiza glabra Linn. Unani Res, 2011. 1: p. 1-11.
6. [6] Mayhoff, C., C. Plini Secundi Naturalis historiae libri XXXVII: Libri XXXI-XXXVII. Vol. 5. 1897: In aedibus BG Teubneri.
7. [7] Hort, A., Enquiry into plants and minor works on odours and weather signs, with an English translation by Sir Arthur Hort, bart. 1916.
8. [8] Asl, M.N. and H. Hosseinzadeh, Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 2008. 22(6): p. 709-724.

9. [9] Gürhan, G. and E. Nurten, Halk arasında hemoroit tedavisinde kullanılan bitkiler-I. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, 2004(1): p. 37-60.
10. [10] AYANOĞLU, F., A. MERT, and D.A. KAYA, Hatay yöresinde halk arasinda kullanilan bazi önemli tibbi ve kokulu bitkilerin tespiti ve toplanmasi. DERGİSİ, 1999: p. 101.
11. [11] EMA. Liquiritiae radix. 2007; Available from: https://www.ema.europa.eu/en/medicines/herbal/liquiritiae-radix#overview-section.
12. [12] ESCOP. Table of herb-drug interactions based on the monographs of ESCOP. 2003; Available from: https://escop.com/interactions/.
13. [13] TITCK. Tıbbi Bitki Monografları. 2020; Available from: https://www.titck.gov.tr/dinamikmodul/51.
14. [14] Lakshmi, T. and R. Geetha, Glycyrrhiza glabra Linn. commonly known as licorice: a therapeutic review. Int J Pharm Pharm Sci, 2011. 3(4): p. 20-5.
15. [15] Hayashi, H. and H. Sudo, Economic importance of licorice. Plant Biotechnology, 2009. 26(1): p. 101-104.
16. [16] Bradley, P., British herbal compendium. Volume 2: a handbook of scientific information of widely used plant drugs. 2006: British Herbal Medicine Association.
17. [17] Yamamura, Y., et al., Pharmacokinetic profile of glycyrrhizin in healthy volunteers by a new high‐performance liquid chromatographic method. Journal of pharmaceutical sciences, 1992. 81(10): p. 1042-1046.
18. [18] Tamir, S., et al., Estrogen-like activity of glabrene and other constituents isolated from Radix Liquiritiae. The Journal of steroid biochemistry and molecular biology, 2001. 78(3): p. 291-298.
19. [19] Batiha, G.E.-S., et al., Traditional uses, bioactive chemical constituents, and pharmacological and toxicological activities of Glycyrrhiza glabra L.(Fabaceae). Biomolecules, 2020. 10(3).
20. [20] Fukai, T., et al., Four isoprenoid-substituted flavonoids from Glycyrrhiza aspera. Phytochemistry, 1994. 36(1): p. 233-236.
21. [21] Chouitah, O., et al., Chemical composition and antimicrobial activities of the essential oil from Glycyrrhiza glabra leaves. Journal of Essential Oil Bearing Plants, 2011. 14(3): p. 284-288.
22. [22] Kameoka, H. and K. Nakai, Components of essential oil from the root of Glycyrrhiza glabra. Journal of the Agricultural Chemical Society of Japan (Japan), 1987.
23. [23] Williamson, E., Potter’s cyclopedia of herbal medicine. CW Daniel, Saffron Walden, 2003: p. 269-271.
24. [24] Kir’yalov, N., New Triterpene Acids from Glycyrrhiza. Vop. Izuch. Ispol’z. Solodki v SSSR, 1966. 123.
25. [25] Kitagawa, I., et al., On the constituents of the roots of Glycyrrhiza uralensis Fischer from northeastern China.(1). Licorice-saponins A3, B2, and C2. Chem Pharm Bull, 1993. 41: p. 43-49.
26. [26] Lu, Z., et al., The chemical constituents of Glycyrrhiza aspera root. Journal of Integrative Plant Biology, 1991. 33(2).
27. [27] Song, W., et al., Uralsaponins M–Y, antiviral triterpenoid saponins from the roots of Glycyrrhiza uralensis. Journal of natural products, 2014. 77(7): p. 1632-1643.
28. [28] Schmid, C., et al., Saponins from European Radix Liquiritiaes (Glycyrrhiza glabra). Journal of natural products, 2018. 81(8): p. 1734-1744.
29. [29] De Simone, F., et al., Anti-HIV aromatic compounds from higherplants. Bioactive Compounds from Natural Sources, 2001: p. 305.
30. [30] Hayashi, H., et al., Flavonoid variation in the leaves of Glycyrrhiza glabra. Phytochemistry, 1996. 42(3): p. 701-704.
31. [31] Kinoshita, T., Y. Tamura, and K. Mizutani, The isolation and structure elucidation of minor isoflavonoids from licorice of Glycyrrhiza glabra origin. Chemical and pharmaceutical bulletin, 2005. 53(7): p. 847-849.
32. [32] Jahan, Y. and H. Siddiqui, Study of antitussive potential of Glycyrrhiza glabra and Adhatoda vasica using a cough model induced by sulphur dioxide gas in mice. International journal of Pharmaceutical Sciences and research, 2012. 3(6): p. 1668.
33. [33] Anderson, D.M. and W. Smith, The antitussive activity of glycyrrhetinic acid and its derivatives. Journal of Pharmacy and Pharmacology, 1961. 13(1): p. 396-404.
34. [34] Chakotiya, A.S., et al., Alternative to antibiotics against Pseudomonas aeruginosa: Effects of Glycyrrhiza glabra on membrane permeability and inhibition of efflux activity and biofilm formation in Pseudomonas aeruginosa and its in vitro time-kill activity. Microbial pathogenesis, 2016. 98: p. 98-105.
35. [35] Kuang, Y., et al., Antitussive and expectorant activities of licorice and its major compounds. Bioorganic & medicinal chemistry, 2018. 26(1): p. 278-284.
36. [36] Račková, L., et al., Mechanism of anti-inflammatory action of liquorice extract and glycyrrhizin. Natural product research, 2007. 21(14): p. 1234-1241.
37. [37] Lateef, M., et al., Evaluation of antioxidant and urease inhibition activities of roots of Glycyrrhiza glabra. Pak J Pharm Sci, 2012. 25(1): p. 99-102.
38. [38] Visavadiya, N.P., B. Soni, and N. Dalwadi, Evaluation of antioxidant and anti-atherogenic properties of Glycyrrhiza glabra root using in vitro models. International journal of food sciences and nutrition, 2009. 60(sup2): p. 135-149.
39. [39] Di Mambro, V.M. and M.J. Fonseca, Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts. Journal of Pharmaceutical and Biomedical Analysis, 2005. 37(2): p. 287-295.
40. [40] Biondi, D.M., C. Rocco, and G. Ruberto, New Dihydrostilbene Derivatives from the Leaves of Glycyrrhiza g labra and Evaluation of Their Antioxidant Activity. Journal of natural products, 2003. 66(4): p. 477-480.
41. [41] Cheel, J., et al., Free radical-scavenging, antioxidant and immunostimulating effects of a licorice infusion (Glycyrrhiza glabra L.). Food Chemistry, 2010. 122(3): p. 508-517.
42. [42] Li, X.-L., et al., Antioxidant status and immune activity of glycyrrhizin in allergic rhinitis mice. International journal of molecular sciences, 2011. 12(2): p. 905-916.
43. [43] Zhang, C.-H., et al., Purification, partial characterization and antioxidant activity of polysaccharides from Glycyrrhiza uralensis. International journal of biological macromolecules, 2015. 79: p. 681-686.
44. [44] Mutaillifu, P., et al., Structural characterization and antioxidant activities of a water soluble polysaccharide isolated from Glycyrrhiza glabra. International journal of biological macromolecules, 2020. 144: p. 751-759.
45. [45] Pompei, R., et al., Glycyrrhizic acid inhibits virus growth and inactivates virus particles. Nature, 1979. 281(5733): p. 689-690.
46. [46] Badam, L., In vitro antiviral activity of indigenous glycyrrhizin, licorice and glycyrrhizic acid (Sigma) on Japanese encephalitis virus. The Journal of communicable diseases, 1997. 29(2): p. 91-99.
47. [47] Ashraf, A., et al., In vivo antiviral potential of Glycyrrhiza glabra extract against Newcastle disease virus. Pakistan journal of pharmaceutical sciences, 2017. 30.
48. [48] Sekizawa, T., K. Yanagi, and Y. I toyama, Glycyrrhizin increases survival of mice with herpes simplex encephalitis. Acta virologica, 2001. 45(1): p. 51-54.
49. [49] Mori, K., et al., Effects of glycyrrhizin (SNMC: Stronger Neo-Minophagen C®) in hemophilia patients with HIV-1 infection. The Tohoku journal of experimental medicine, 1990. 162(2): p. 183-193.
50. [50] van Rossum, T.G., et al., Pharmacokinetics of intravenous glycyrrhizin after single and multiple doses in patients with chronic hepatitis C infection. Clinical therapeutics, 1999. 21(12): p. 2080-2090.
51. [51] Rossum, T.V. and R.D. Man, Glycyrrhizin as a potential treatment for chronic hepatitis C. Alimentary pharmacology & therapeutics, 1998. 12(3): p. 199-205.
52. [52] Huan, C.-c., et al., Glycyrrhizin inhibits porcine epidemic diarrhea virus infection and attenuates the proinflammatory responses by inhibition of high mobility group box-1 protein. Archives of virology, 2017. 162(6): p. 1467-1476.
53. [53] Ashfaq, U.A., et al., Glycyrrhizin as antiviral agent against Hepatitis C Virus. Journal of translational medicine, 2011. 9(1): p. 1-7.
54. [54] Laconi, S., M.A. Madeddu, and R. Pompei, Autophagy activation and antiviral activity by a licorice triterpene. Phytotherapy Research, 2014. 28(12): p. 1890-1892.
55. [55] Mazumder, P.M., et al., Evaluation of immunomodulatory activity of Glycyrhiza glabra L roots in combination with zing. Asian pacific journal of tropical biomedicine, 2012. 2(1): p. S15-S20.
56. [56] LIU, L.-p., C.-a. REN, and H.-y. ZHAO, Research Progress on Immunomodulatory Effects of Glycyrrhizin [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2010. 6.
57. [57] Ayeka, P.A., et al., Immunomodulatory and anticancer potential of Gan cao (Glycyrrhiza uralensis Fisch.) polysaccharides by CT-26 colon carcinoma cell growth inhibition and cytokine IL-7 upregulation in vitro. BMC complementary and alternative medicine, 2016. 16(1): p. 1-8.
58. [58] Nitalikar, M.M., et al., Studies of antibacterial activities of Glycyrrhiza glabra root extract. Int J Pharm Tech Res, 2010. 2(1): p. 899-901.
59. [59] Haraguchi, H., et al., Mode of antibacterial action of retrochalcones from Glycyrrhiza inflata. Phytochemistry, 1998. 48(1): p. 125-129.
60. [60] Sultana, S., et al., Antimicrobial, cytotoxic and antioxidant activity of methanolic extract of Glycyrrhiza glabra. Agric Biol JN Am, 2010. 1(5): p. 957-60.
61. [61] Chopra, P., et al., Antimicrobial and antioxidant activities of methanol extract roots of Glycyrrhiza glabra and HPLC analysis. Int J Pharm Pharmacol Sci, 2013. 5(2): p. 157-160.
62. [62] Fukai, T., et al., Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus. Fitoterapia, 2002. 73(6): p. 536-539.
63. [63] Malek, J.M. and K. Ghazvini, In vitro susceptibility of Helicobacter pylori to licorice extract. 2007.
64. [64] Ram, H.A., et al., Formulation and evaluation of floating tablets of liquorice extract. Pharmacognosy research, 2010. 2(5): p. 304.
65. [65] Monder, C., et al., Licorice inhibits corticosteroid 1lβ-dehydrogenase of rat kidney and liver: in vivo and in vitro studies. Endocrinology, 1989. 125(2): p. 1046-1053.
66. [66] Aly, A.M., L. Al-Alousi, and H.A. Salem, Licorice: a possible anti-inflammatory and anti-ulcer drug. Aaps Pharmscitech, 2005. 6(1): p. E74-E82.
67. [67] Jalilzadeh-Amin, G., et al., Antiulcer properties of Glycyrrhiza glabra L. extract on experimental models of gastric ulcer in mice. Iranian journal of pharmaceutical research: IJPR, 2015. 14(4): p. 1163.
68. [68] Parle, M., D. Dhingra, and S. Kulkarni, Memory-strengthening activity of Glycyrrhiza glabra in exteroceptive and interoceptive behavioral models. Journal of Medicinal Food, 2004. 7(4): p. 462-466.
69. [69] Chakravarthi, K.K. and R. Avadhani, Beneficial effect of aqueous root extract of Glycyrrhiza glabra on learning and memory using different behavioral models: An experimental study. Journal of natural science, biology, and medicine, 2013. 4(2): p. 420.
70. [70] Lee, C.S., et al., 18β-Glycyrrhetinic acid induces apoptotic cell death in SiHa cells and exhibits a synergistic effect against antibiotic anti-cancer drug toxicity. Life sciences, 2008. 83(13-14): p. 481-489.
71. [71] Sharma, V., R. Agrawal, and V.K. Shrivastava, Assessment of median lethal dose and anti-mutagenic effects of Glycyrrhiza glabra root extract against chemically induced micronucleus formation in Swiss albino mice. International Journal of Basic & Clinical Pharmacology, 2014. 3(2): p. 292.
72. [72] Chin, Y.-W., et al., Anti-oxidant constituents of the roots and stolons of licorice (Glycyrrhiza glabra). Journal of agricultural and food chemistry, 2007. 55(12): p. 4691-4697.
73. [73] Deng, Q.-P., et al., Effects of glycyrrhizin in a mouse model of lung adenocarcinoma. Cellular Physiology and Biochemistry, 2017. 41(4): p. 1383-1392.
74. [74] Nagaraj, S.R.M., et al., MTA1 induced angiogenesis, migration and tumor growth is inhibited by Glycyrrhiza glabra. IOSR J Pharmacy, 2012. 2: p. 34-43.
75. [75] Hasan, S.K., et al., Chemopreventive effect of 18β-glycyrrhetinic acid via modulation of inflammatory markers and induction of apoptosis in human hepatoma cell line (HepG2). Molecular and cellular biochemistry, 2016. 416(1-2): p. 169-177.
76. [76] Kim, K.J., et al., The anti‐angiogenic activities of glycyrrhizic acid in tumor progression. Phytotherapy Research, 2013. 27(6): p. 841-846.
77. [77] Lin, D., et al., Involvement of BID translocation in glycyrrhetinic acid and 11-deoxy glycyrrhetinic acid-induced attenuation of gastric cancer growth. Nutrition and cancer, 2014. 66(3): p. 463-473.
78. [78] Yo, Y.-T., et al., Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway. Journal of agricultural and food chemistry, 2009. 57(18): p. 8266-8273.
79. [79] Zhang, Z., et al., Molecular mechanisms underlying the anticancer activities of licorice flavonoids. Journal of Ethnopharmacology, 2020: p. 113635.
80. [80] Sharma, G., et al., 18β‐glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF‐7 cells. Journal of cellular physiology, 2012. 227(5): p. 1923-1931.
81. [81] Dhingra, D. and A. Sharma, Antidepressant-like activity of Glycyrrhiza glabra L. in mouse models of immobility tests. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2006. 30(3): p. 449-454.
82. [82] Tawata, M., et al., Anti-platelet action of isoliquiritigenin, an aldose reductase inhibitor in licorice. European journal of pharmacology, 1992. 212(1): p. 87-92.
83. [83] Adamyan, T.I., et al., Effect of Radix Liquiritiae on peripheral blood indexes upon vibration exposure. Bulletin of experimental biology and medicine, 2005. 140(2): p. 197-200.
84. [84] Yu, S.M. and S.C. Kuo, Vasorelaxant effect of isoliquiritigenin, a novel soluble guanylate cyclase activator, in rat aorta. British journal of pharmacology, 1995. 114(8): p. 1587-1594.
85. [85] Upadhyay, S., A.K. Mantha, and M. Dhiman, Glycyrrhiza glabra (Licorice) root extract attenuates doxorubicin-induced cardiotoxicity via alleviating oxidative stress and stabilising the cardiac health in H9c2 cardiomyocytes. Journal of ethnopharmacology, 2020. 258: p. 112690.
86. [86] Zhai, C.-l., et al., Glycyrrhizin protects rat heart against ischemia-reperfusion injury through blockade of HMGB1-dependent phospho-JNK/Bax pathway. Acta Pharmacologica Sinica, 2012. 33(12): p. 1477-1487.
87. [87] Isbrucker, R. and G. Burdock, Risk and safety assessment on the consumption of Radix Liquiritiae (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin. Regulatory Toxicology and Pharmacology, 2006. 46(3): p. 167-192.
88. [88] Koga, K., et al., Intestinal absorption and biliary elimination of glycyrrhizic acid diethyl ester in rats. Drug design, development and therapy, 2013. 7: p. 1235.
89. [89] Al-Snafi, A.E., A review on Fagopyrum esculentum: A potential medicinal plant. IOSR Journal of Pharmacy, 2017. 7(3): p. 21-32.