The Review of In Vitro and In Vivo Studies over the Glycyrrhizic Acid as Natural Remedy Option for Treatment of Allergic Asthma

  • Saloomeh Fouladi Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  • Mohsen Masjedi Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  • Mazdak Ganjalikhani Hakemi Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  • Nahid Eskandari Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Keywords: Allergic asthma, Glycyrrhizic acid, Herbal medicine, Inflammation

Abstract

Allergic asthma is the most common type of allergy which have become increasingly prevalent in all around the world. Airway eosinophilic inflammation is a major feature of allergic asthma. Glycyrrhiza uralensis (licorice) is one of the regular herbs in traditional Chinese medicine (TCM) as it has many effects on the immune system such as anti-inflammatory and immune regulatory activity; antiviral and antitumor effects. This review focuses on the "licorice” components, mainly glycyrrhizic acid (GA) and derivatives structure that evaluate its effects on the allergic asthma. We performed searching articles in Pubmed, Web of Science, and Scopus data bank from 1990 to 2017. The search syntax were: "glycyrrhizin" OR " glycyrrhizic acid" OR " glycyrrhizinic acid" OR" glycyrrhiza glabra" OR " liquorice root" OR "G. glabra" OR "glycyrrhizic Acid" AND "allergic asthma"  OR "bronchial asthma" OR "asthma, bronchial" OR "airway hyper-responsiveness" OR "airway inflammation".  Several molecular mechanisms and inflammatory mediators may possibly be responsible for efficacy of glycyrrhizin. Some in vitro studies indicated to the fact that possible mechanisms of anti-inflammatory effects could be through reduction of pro-inflammatory mediator's synthesis that motivates eosinophil, basophils and mast cells to release cytokines for the differentiation of T helper cells into Th2 cells to secrete interleukins. Furthermore, some transcription factors such as NF-κB, STAT6 and HDAC2 go between modulations of anti-asthmatic effects. The last but not the least it can be said that glycyrrhizin is potentially a good herbal drug with the lower most adverse effects for asthma treatment.

References

References:

1. Yawn BP. Factors accounting for asthma variability: achieving optimal symptom control for individual patients. Prim Care Respir J. 2008;17(3):138-47.

2. Anandan C, Nurmatov U, van Schayck OC, Sheikh A. Is the prevalence of asthma declining? Systematic review of epidemiological studies. Allergy. 2010;65(2):152-67.

3. Evans R, 3rd, Mullally DI, Wilson RW, Gergen PJ, Rosenberg HM, Grauman JS, et al. National trends in the morbidity and mortality of asthma in the US. Prevalence, hospitalization and death from asthma over two decades: 1965-1984. Chest. 1987;91(6 Suppl):65S-74S.

4. Disease GBD, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1545-602.

5. Holt PG, Macaubas C, Stumbles PA, Sly PD. The role of allergy in the development of asthma. Nature. 1999;402(6760 Suppl):B12-7.

6. Pauwels R. The relationship between airway inflammation and bronchial hyperresponsiveness. Clin Exp Allergy. 1989;19(4):395-8.

7. Holgate ST. The epidemic of allergy and asthma. Nature. 1999;402(6760 Suppl):B2-4.

8. Webb DC, McKenzie AN, Koskinen AM, Yang M, Mattes J, Foster PS. Integrated signals between IL-13, IL-4, and IL-5 regulate airways hyperreactivity. J Immunol. 2000;165(1):108-13.

9. Farahani R, Sherkat R, Hakemi MG, Eskandari N, Yazdani R. Cytokines (interleukin-9, IL-17, IL-22, IL-25 and IL-33) and asthma. Adv Biomed Res. 2014;3:127.

10. Martin H, Taube C. Regulatory T cells and regulation of allergic airway disease. Am J Clin Exp Immunol. 2012;1(2):166-78.

11. Hossny E, Rosario N, Lee BW, Singh M, El-Ghoneimy D, SOH JY, et al. The use of inhaled corticosteroids in pediatric asthma: update. World Allergy Organization Journal. 2016;9(1):26.

12. Scott JP, Peters-Golden M. Antileukotriene agents for the treatment of lung disease. Am J Respir Crit Care Med. 2013;188(5):538-44.

13. Eskandari N, Wickramasinghe T, Peachell PT. Effects of phosphodiesterase inhibitors on interleukin‐4 and interleukin‐13 generation from human basophils. British journal of pharmacology. 2004;142(8):1265-72.

14. Bastan R, Eskandari N, H JA, P TP. Effects of fostriecin on beta2-adrenoceptor-driven responses in human mast cells. Journal of immunotoxicology. 2017;14(1):60-5.

15. Eskandari N, Bastan R, Esfahani SHZ, Peachell PT. The effect of cyclic nucleotide analog drugs on the mediators release from basophils. Advanced biomedical research. 2015;4.

16. Mohammadi-Shahrokhi V, Rezaei A, Andalib A, Rahnama A, Jafarzadeh A, Eskandari N. Immunomodulatory Effects of Adjuvants CPG, MPLA, and BCG on the Derp2-Induced Acute Asthma at Early Life in an Animal Model of BALB/c Mice. Inflammation. 2016:1-16.

17. Mohammadi-Shahrokhi V, Rezaei A, Andalib A, Rahnama A, Jafarzadeh A, Eskandari N. Improvement of Th1/Th2 and Th1/Treg Imbalances by Adjutants CPG, MPLA and BCG in a Model of Acute Asthma Induced By Allergen Derp2 in BALB/c Mice. Iranian Red Crescent Medical Journal. 2016(In Press).

18. Bielory L, Lupoli K. Herbal Interventions in Asthma and Allergy. Journal of Asthma. 1999;36(1):1-65.

19. Huntley A, Ernst E. Herbal medicines for asthma: a systematic review. Thorax. 2000;55(11):925-9.

20. B Cota B, M Bertollo C, M de Oliveira D. Anti-allergic potential of herbs and herbal natural products-activities and patents. Recent patents on endocrine, metabolic & immune drug discovery. 2013;7(1):26-56.

21. Yang R, Wang LQ, Yuan BC, Liu Y. The Pharmacological Activities of Licorice. Planta medica. 2015;81(18):1654-69.

22. Parvaiz M, Hussain K, Khalid S, Hussnain N, Iram N, Hussain Z, et al. A review: Medicinal importance of Glycyrrhiza glabra L.(Fabaceae Family). Global Journal of Pharmacology. 2014;8(1):8-13.

23. Liut HM, Akiyama T, Sugimoto N, Maitani T. Isolation and identification of main constituents in an enzymatically hydrolysed licorice extract sweetener. Food Addit Contam. 2001;18(4):281-4.

24. Ernst E. Complementary therapies for asthma: what patients use. Journal of Asthma. 1998;35(8):667-71.

25. Blanc PD, Trupin L, Earnest G, Katz PP, Yelin EH, Eisner MD. Alternative therapies among adults with a reported diagnosis of asthma or rhinosinusitis: data from a population-based survey. CHEST Journal. 2001;120(5):1461-7.

26. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. Jama. 1998;280(18):1569-75.

27. Fiore C, Eisenhut M, Ragazzi E, Zanchin G, Armanini D. A history of the therapeutic use of liquorice in Europe. Journal of ethnopharmacology. 2005;99(3):317-24.

28. Li XM. Treatment of asthma and food allergy with herbal interventions from traditional chinese medicine. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine. 2011;78(5):697-716.

29. Ram A, Mabalirajan U, Das M, Bhattacharya I, Dinda AK, Gangal SV, et al. Glycyrrhizin alleviates experimental allergic asthma in mice. Int Immunopharmacol. 2006;6(9):1468-77.

30. Tamir S, Eizenberg M, Somjen D, Izrael S, Vaya J. Estrogen-like activity of glabrene and other constituents isolated from licorice root. J Steroid Biochem Mol Biol. 2001;78(3):291-8.

31. Park SY, Kwon SJ, Lim SS, Kim JK, Lee KW, Park JH. Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells. International journal of molecular sciences. 2016;17(6).

32. Park SY, Kim EJ, Choi HJ, Seon MR, Lim SS, Kang YH, et al. Anti-carcinogenic effects of non-polar components containing licochalcone A in roasted licorice root. Nutrition research and practice. 2014;8(3):257-66.

33. Kakegawa H, Matsumoto H, Satoh T. Inhibitory effects of some natural products on the activation of hyaluronidase and their anti-allergic actions. Chem Pharm Bull (Tokyo). 1992;40(6):1439-42.

34. Friis-Møller A, Chen M, Fuursted K, Christensen SB, Kharazmi A. In vitro antimycobacterial and antilegionella activity of licochalcone A from Chinese licorice roots. Planta medica. 2002;68(05):416-9.

35. Sasaki H, Takei M, Kobayashi M, Pollard RB, Suzuki F. Effect of glycyrrhizin, an active component of licorice roots, on HIV replication in cultures of peripheral blood mononuclear cells from HIV-seropositive patients. Pathobiology. 2002;70(4):229-36.

36. Hosseinzadeh H, Nassiri-Asl M. Pharmacological Effects of Glycyrrhiza spp. and Its Bioactive Constituents: Update and Review. Phytotherapy research : PTR. 2015;29(12):1868-86.

37. Zhou YQ, Yu H, Li Y, Sun SQ, Zhao RH, Chen SL. [Classification of licorice based on inorganic elements characteristics]. Guang pu xue yu guang pu fen xi = Guang pu. 2010;30(4):1101-4.

38. Wang J, Zhang J, Gao W, Wang Q, Yin S, Liu H, et al. Identification of triterpenoids and flavonoids, step-wise aeration treatment as well as antioxidant capacity of Glycyrrhiza uralensis Fisch. cell. Industrial Crops and Products. 2013;49:675-81.

39. Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N. Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health. Biotechnology journal. 2007;2(10):1214-34.

40. Tolstikov G, Baltina L, Grankina V, Kondratenko R, Tolstikova T. [Licorice: biodiversity, application in medicine]. 2007.

41. Kitagawa I. Licorice root. A natural sweetener and an important ingredient in Chinese medicine. Pure and applied chemistry. 2002;74(7):1189-98.

42. Shibata S. A drug over the millennia: pharmacognosy, chemistry, and pharmacology of licorice. Journal of the Pharmaceutical Society of Japan. 2000;120(10):849-62.

43. Kaur R, Kaur H, Dhindsa AS. Glycyrrhiza glabra: a phytopharmacological review. International Journal of Pharmaceutical Sciences and Research. 2013;4(7):2470.

44. Puja T. DEVELOPMENT AND EVALUATION OF A POLYHERBAL PREPARATION. Journal of Advanced Scientific Research. 2012;3(1).

45. Damle M. Glycyrrhiza glabra (liquorice)-a potent medicinal herb. International of Herbal Medicine. 2014;2(2):132-6.

46. Houssen ME, Ragab A, Mesbah A, El-Samanoudy AZ, Othman G, F.Moustafa A, et al. Natural anti-inflammatory products and leukotriene inhibitors as complementary therapy for bronchial asthma. Clinical Biochemistry. 2010;43(10–11):887-90.

47. Clark CE, Arnold E, Lasserson TJ, Wu T. Herbal interventions for chronic asthma in adults and children: a systematic review and meta-analysis. Prim Care Respir J. 2010;19(4):307-14.

48. Gao H, Sun Z, Xiao C, Zheng X, Zhang Y. The metabonomic study of Shaoyao-Gancao decoction in a rat model of acute bronchial asthma by 1 H NMR. Analytical Methods. 2016;8(3):570-81.

49. Yu J-Y, Ha JY, Kim K-M, Jung Y-S, Jung J-C, Oh S. Anti-Inflammatory Activities of Licorice Extract and Its Active Compounds, Glycyrrhizic Acid, Liquiritin and Liquiritigenin, in BV2 Cells and Mice Liver. Molecules. 2015;20(7):13041-54.

50. Jayaprakasam B, Yang N, Wen M-C, Wang R, Goldfarb J, Sampson H, et al. Constituents of the anti-asthma herbal formula ASHMI™ synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro. Journal of integrative medicine. 2013;11(3):195-205.

51. Takei H, Baba Y, Hisatsune A, Katsuki H, Miyata T, Yokomizo K, et al. Glycyrrhizin Inhibits Interleukin-8 Production and Nuclear Factor–κB Activity in Lung Epithelial Cells, but Not Through Glucocorticoid Receptors. Journal of Pharmacological Sciences. 2008;106(3):460-8.

52. Kao T-C, Shyu M-H, Yen G-C. Glycyrrhizic acid and 18β-glycyrrhetinic acid inhibit inflammation via PI3K/Akt/GSK3β signaling and glucocorticoid receptor activation. Journal of agricultural and food chemistry. 2010;58(15):8623-9.

53. Liu B, Yang J, Wen Q, Li Y. Isoliquiritigenin, a flavonoid from licorice, relaxes guinea-pig tracheal smooth muscle in vitro and in vivo: Role of cGMP/PKG pathway. European Journal of Pharmacology. 2008;587(1–3):257-66.

54. Nishimoto Y, Hisatsune A, Katsuki H, Miyata T, Yokomizo K, Isohama Y. Glycyrrhizin attenuates mucus production by inhibition of MUC5AC mRNA expression in vivo and in vitro. Journal of Pharmacological Sciences. 2010;113(1):76-83.

55. Al-Dujaili EA, Kenyon C, Nicol M, Mason J. Liquorice and glycyrrhetinic acid increase DHEA and deoxycorticosterone levels in vivo and in vitro by inhibiting adrenal SULT2A1 activity. Molecular and cellular endocrinology. 2011;336(1):102-9.

56. Liu C, Weir D, Busse P, Yang N, Zhou Z, Emala C, et al. The Flavonoid 7, 4'- Dihydroxyflavone Inhibits MUC5AC Gene Expression, Production, and Secretion Via Regulation of NF-κB, STAT6 and HDAC2. Phytotherapy research : PTR. 2015;29(6):925-32.

57. Jayaprakasam B, Doddaga S, Wang R, Holmes D, Goldfarb J, Li X-M. Licorice flavonoids inhibit eotaxin-1 secretion by human fetal lung fibroblasts in vitro. Journal of agricultural and food chemistry. 2009;57(3):820-5.

58. Selyutina OY, Polyakov N, Korneev D, Zaitsev B. Influence of glycyrrhizin on permeability and elasticity of cell membrane: perspectives for drugs delivery. Drug delivery. 2016;23(3):848-55.

59. Aggarwal BB, Prasad S, Reuter S, Kannappan R, Yadev VR, Park B, et al. Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: “Reverse Pharmacology” and “Bedside to Bench” Approach. Current drug targets. 2011;12(11):1595-653.

60. Boskabady MH, Neamati A, Hazrati SM, Khakzad MR, Moosavi SH, Gholamnezhad Z. The preventive effects of natural adjuvants, G2 and G2F on tracheal responsiveness and serum IL-4 and IFN-³ (th1/th2 balance) in sensitized guinea pigs. Clinics. 2014;69:491-6.

61. Isbrucker R, Burdock G. 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. Regulatory Toxicology and Pharmacology. 2006;46(3):167-92.

62. Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. Journal of ethnopharmacology. 2013;150(3):781-90.

63. Hocaoglu AB, Karaman O, Erge DO, Erbil G, Yilmaz O, Bagriyanik A, et al. Glycyrrhizin and long-term histopathologic changes in a murine model of asthma. Current Therapeutic Research. 2011;72(6):250-61.

64. Yang Y, Shi Q, Liu Z, Li R-j, Pan P-w, Hou Y-y, et al. The synergistic anti-asthmatic effects of glycyrrhizin and salbutamol. Acta Pharmacol Sin. 2010;31(4):443-9.

65. Shi Q, Hou Y, Yang Y, Bai G. Protective Effects of Glycyrrhizin against. BETA. 2-Adrenergic Receptor Agonist-Induced Receptor Internalization and Cell Apoptosis. Biological and Pharmaceutical Bulletin. 2011;34(5):609-17.

66. Wu Q, Tang Y, Hu X, Wang Q, Lei W, Zhou L, et al. Regulation of Th1/Th2 balance through OX40/OX40L signalling by glycyrrhizic acid in a murine model of asthma. Respirology. 2016;21(1):102-11.

67. Wu Q, Tang Y, Zhang J, Hu X, Wang Q, Huang J. [Therapeutic effects of glycyrrhizic acid on asthma airway inflammation in mice and its mechanism]. Zhonghua yi xue za zhi. 2014;94(42):3338-44.

68. Ma C, Ma Z, Liao X-l, Liu J, Fu Q, Ma S. Immunoregulatory effects of glycyrrhizic acid exerts anti-asthmatic effects via modulation of Th1/Th2 cytokines and enhancement of CD4+ CD25+ Foxp3+ regulatory T cells in ovalbumin-sensitized mice. Journal of ethnopharmacology. 2013;148(3):755-62.

69. Shin Y-W, Bae E-A, Lee B, Lee SH, Kim JA, Kim Y-S, et al. In vitro and in vivo antiallergic effects of Glycyrrhiza glabra and its components. Planta medica. 2007;73(03):257-61.

70. Zhang T, Srivastava K, Wen MC, Yang N, Cao J, Busse P, et al. Pharmacology and immunological actions of a herbal medicine ASHMITM on allergic asthma. Phytotherapy Research. 2010;24(7):1047-55.

71. Zhang S, Zeng X, He S. An update on anti-allergic patents granted in China: 2009–2011. Expert opinion on therapeutic patents. 2012;22(7):715-34.

72. Srivastava K, Zhang T, Yang N, Sampson H, Li X-M. Anti‐Asthma Simplified Herbal Medicine Intervention‐induced long‐lasting tolerance to allergen exposure in an asthma model is interferon‐γ, but not transforming growth factor‐β dependent. Clinical & Experimental Allergy. 2010;40(11):1678-88.

73. Chang H-C, Gong C-C, Chen J-L, Mak O-T. Inhibitory effects of inhaled complex traditional Chinese medicine on early and late asthmatic responses induced by ovalbumin in sensitized guinea pigs. BMC complementary and alternative medicine. 2011;11(1):1.

74. Yang N, Patil S, Zhuge J, Wen MC, Bolleddula J, Doddaga S, et al. Glycyrrhiza uralensis Flavonoids Present in Anti‐Asthma Formula, ASHMITM, Inhibit Memory Th2 Responses in Vitro and in Vivo. Phytotherapy Research. 2013;27(9):1381-91.

75. Wen M-C, Wei C-H, Hu Z-Q, Srivastava K, Ko J, Xi S-T, et al. Efficacy and tolerability of antiasthma herbal medicine intervention in adult patients with moderate-severe allergic asthma. Journal of allergy and clinical immunology. 2005;116(3):517-24.

76. Kelly-Pieper K, Patil SP, Busse P, Yang N, Sampson H, Li X-M, et al. Safety and Tolerability of an Antiasthma Herbal Formula (ASHMI™) in adult subjects with asthma: a randomized, double-blinded, placebo-controlled, dose-escalation Phase I study. The Journal of Alternative and Complementary Medicine. 2009;15(7):735-43.

Published
2019-01-22
How to Cite
1.
Fouladi S, Masjedi M, Ganjalikhani Hakemi M, Eskandari N. The Review of In Vitro and In Vivo Studies over the Glycyrrhizic Acid as Natural Remedy Option for Treatment of Allergic Asthma. Iran J Allergy Asthma Immunol. 17(5):1-1.
Section
Review Article(s)