Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: Potential pharmacological applications with mechanistic insight.

Abd, 2015, Effect of Glycyrrhiza glabra (L.) on antigen induced arthritis in mice model, Iraqi JMS, 13, 129 Abdel-Wahab, 2021, A licorice roots extract induces apoptosis and cell cycle arrest and improves metabolism via regulating MiRNAs in liver cancer cells, Nutr. Cancer, 73, 1047, 10.1080/01635581.2020.1783329 Abtahifroushani, 2014, Immunomodulatory effects by hydroalcoholic liquorice root extracts, J. Adv Med. Biomed. Res., 22, 112 Adithya, 2021, The plausible role of Indian traditional medicine in combating corona virus (SARS-CoV 2): a mini-review, Curr. Pharm. Biotechnol., 22, 906, 10.2174/1389201021666200807111359 Alagawany, 2019, Use of licorice (Glycyrrhiza glabra) herb as a feed additive in poultry: current knowledge and prospects, Animals, 9, 536, 10.3390/ani9080536 Alexyuk, 2019, Adjuvant activity of multimolecular complexes based on Glycyrrhiza glabra saponins, lipids, and influenza virus glycoproteins, Arch. Virol., 164, 1793, 10.1007/s00705-019-04273-2 Aliavi, 2002, Use of glycyrrhiza extract in restoring local nonspecific defense of the lungs in patients with chronic obstructive bronchitis, Vopr. Kurortol. Fizioter. Lech. Fiz. Kult., 2, 40 Aly, 2005, Licorice: a possible anti-inflammatory and anti-ulcer drug, AAPS Pharm. Sci. Tech., 6, E74, 10.1208/pt060113 Anagha, 2014, Scope of Glycyrrhiza glabra (Yashtimadhu) as an antiviral agent: a review, Int. J. Curr. Microbiol. App. Sci., 3, 657 Anand, 2021, Medicinal plants, phytochemicals, and herbs to combat viral pathogens including SARS-CoV-2, Molecules, 26, 1775, 10.3390/molecules26061775 Anderson, 1961, The antitussive activity of glycyrrhetinic acid and its derivatives, J. Pharm. Pharmacol., 1961, 396 Armanini, 2020, Coronavirus-19: possible therapeutic implications of spironolactone and dry extract of Glycyrrhiza glabra L. (Licorice), Front. Pharmacol., 11, 10.3389/fphar.2020.558418 Ashfaq, 2011, Glycyrrhizin as antiviral agent against Hepatitis C Virus, J. Transl. Med., 9, 1, 10.1186/1479-5876-9-112 Ashraf, 2017, In vivo antiviral potential of Glycyrrhiza glabra extract against Newcastle disease virus, Pak. J. Pharm. Sci., 30, 567 Asl, 2008, Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds, Phytother. Res., 22, 709, 10.1002/ptr.2362 Avinash, 2021, In silico screened flavanoids of Glycyrrhiza glabra Inhibit cPLA2 and sPLA2 in LPS stimulated macrophages, Bull. Env. Pharmacol. Life Sciences, 10, 14 Ayeka, 2016, 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 Compl. Alternative Med., 16, 206, 10.1186/s12906-016-1171-4 Ayeka, 2017, The immunomodulatory activities of licorice polysaccharides (Glycyrrhiza uralensis Fisch.) in CT 26 tumor-bearing mice, BMC Compl. Alternative Med., 17, 536, 10.1186/s12906-017-2030-7 Badam, 1997, In vitro antiviral activity of indigenous glycyrrhizin, licorice and glycyrrhizic acid (Sigma) on Japanese encephalitis virus, J. Commun. Dis., 29, 91 Bagherwal, 2009, Immunostimulant activity of aqueous extract roots of Glycyrrhiza glabra, Res. J. Pharmacol. Pharmacodyn., 1, 120 Bailly, 2020, Glycyrrhizin: an alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome?, Pharmacol. Ther., 214, 10.1016/j.pharmthera.2020.107618 Baltina, 2009, Prospects for the creation of new antiviral drugs based on glycyrrhizic acid and its derivatives (a review), Pharm. Chemistry J., 43, 539, 10.1007/s11094-010-0348-2 Bandyopadhyay, 2021, Polypharmacology of some medicinal plant metabolites against SARS-CoV-2 and host targets: molecular dynamics evaluation of NSP9 RNA binding protein, J. Biomol. Struct. Dyn., 9, 1, 10.1080/07391102.2021.1959401 Basar, 2015, Comparative cytotoxicity of Glycyrrhiza glabra roots from different geographical origins against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cells, Phytother. Res., 29, 944, 10.1002/ptr.5329 Batiha, 2020, Traditional uses, bioactive chemical constituents, and pharmacological and toxicological activities of Glycyrrhiza glabra L. (Fabaceae), Biomolecules, 10, 352, 10.3390/biom10030352 Bernela, 2016, Enhancement of anti-inflammatory activity of glycyrrhizic acid by encapsulation in chitosan-katira gum nanoparticles, Eur. J. Pharm. Biopharm., 105, 141, 10.1016/j.ejpb.2016.06.003 Bodet, 2008, A licorice extract reduces lipopolysaccharide-induced proinflammatory cytokine secretion by macrophages and whole blood, J. Periodontol., 79, 1752, 10.1902/jop.2008.080052 Boozari, 2021, Natural products for COVID-19 prevention and treatment regarding to previous coronavirus infections and novel studies, Phytother. Res., 35, 864, 10.1002/ptr.6873 Bordbar, 2012, The effect of glycyrrhizin on maturation and T cell stimulating activity of dendritic cells, Cell. Immunol., 280, 44, 10.1016/j.cellimm.2012.11.013 Bredin, 2019, Liquorice (Glycyrrhiza glabra): the journey of the sweet root from Mesopotamia to England, J. R. Coll. Physicians Edinb., 49, 171, 10.4997/JRCPE.2019.222 Brendler, 2021, Botanical drugs and supplements affecting the immune response in the time of COVID-19: implications for research and clinical practice, Phytother. Res., 35, 3013, 10.1002/ptr.7008 Cao, 2018, The protective effects of 18-β-glycyrrhetinic acid against inflammation microenvironment in gastric tumorigenesis targeting PGE2-EP2 receptor-mediated arachidonic acid pathway, Eur. J. Inflamm., 16, 1, 10.1177/2058739218762993 Chakotiya, 2017, Effect of aquo-alchoholic extract of Glycyrrhiza glabra against Pseudomonas aeruginosa in mice lung infection model, Biomed. Pharmacother., 90, 171, 10.1016/j.biopha.2017.03.055 Chandrasekaran, 2011, Dual inhibitory effect of Glycyrrhiza glabra L (GutGardTM) on COX and LOX products, Phytomedicine, 18, 278, 10.1016/j.phymed.2010.08.001 Chen, 2020, Advances in pharmacological activities and mechanisms of Glycyrrhizic Acid, Curr. Med. Chem., 27, 6219, 10.2174/0929867325666191011115407 Chen, 2020, A novel combination of vitamin C, curcumin and glycyrrhizic acid potentially regulates immune and inflammatory response associated with coronavirus infections: a perspective from system biology analysis, Nutrients, 12, 1193, 10.3390/nu12041193 Cheng, 2008, Macrophage immunomodulatory activity of polysaccharides isolated from Glycyrrhiza uralensis fish, Int. Immunopharmacol., 8, 43, 10.1016/j.intimp.2007.10.006 Cho, 2021, Anti-inflammatory effect of Chrysanthemum zawadskii, peppermint, Glycyrrhiza glabra herbal mixture in lipopolysaccharide-stimulated RAW264.7 macrophages, Mol. Med. Rep., 24, 532, 10.3892/mmr.2021.12171 Chowdhury, 2021, Prospect of biobased antiviral face mask to limit the coronavirus outbreak, Environ. Res., 192, 10.1016/j.envres.2020.110294 Chu, 2012, Licochalcone a inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo, J. Agric. Food Chem., 60, 3947, 10.1021/jf2051587 Ciganovic, 2019, Glycerolic licorice extracts as active cosmeceutical ingredients: extraction optimization, chemical characterization, and biological activity, Antioxidants, 8, 445, 10.3390/antiox8100445 Cinatl, 2003, Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus, Lancet, 361, 2045, 10.1016/S0140-6736(03)13615-X Ciprandi, 2020, HMGB1 in nasal inflammatory diseases: a reappraisal 30 years after its discovery, Expert Rev. Clin. Immunol., 16, 457, 10.1080/1744666X.2020.1752668 Dao, 2011, Chalcones as novel influenza A (H1N1) neuraminidase inhibitors from Glycyrrhiza inflata, Bioorg. Med. Chem. Lett., 21, 294, 10.1016/j.bmcl.2010.11.016 Dastagir, 2016, Review - Glycyrrhiza glabra L. (Liquorice), Pak. J. Pharm. Sci., 29, 1727 De Oliveira, 2014, Animal health: mycotoxins, 358 Diomede, 2021, Can antiviral activity of licorice help fight COVID-19 infection?, Biomolecules, 11, 855, 10.3390/biom11060855 Dziewulska, 2018, The impact of Aloe vera and licorice extracts on selected mechanisms of humoral and cell-mediated immunity in pigeons experimentally infected with PPMV-1, BMC. Vet. Res., 14, 148, 10.1186/s12917-018-1467-3 Ebrahimnezhad, 2016, Decline in immunological responses mediated by dendritic cells in mice treated with 18α-glycyrrhetinic acid, Immunol. Invest, 45, 191, 10.3109/08820139.2015.1113425 Elabd, 2016, Feeding Glycyrrhiza glabra (liquorice) and Astragalus membranaceus (AM) alters innate immune and physiological responses in yellow perch (Perca flavescens), Fish Shellfish Immunol, 54, 374, 10.1016/j.fsi.2016.04.024 Fatima, 2020, Herbal approach for the management of C0VID-19: an overview, Drug Metab. Pers. Ther., 10.1515/dmdi-2020-0150 Feng Yeh, 2013, Water extract of licorice had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines, J. Ethnopharmacol, 148, 466, 10.1016/j.jep.2013.04.040 Finney, 1958, The antiinflammatory activity of glycyrrhetinic acid and derivatives, J. Pharm. Pharmacol., 10, 613 Fiore, 2008, Antiviral effects of Glycyrrhiza species, Phytother. Res., 22, 141, 10.1002/ptr.2295 Fouladi, 2019, 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., 18, 1 Frattaruolo, 2019, Antioxidant and anti-inflammatory activities of flavanones from Glycyrrhiza glabra (L.) (licorice) leaf phyto-complexes: identification of licoflavanone as a modulator of NF-kB/MAPK pathway, Antioxidants, 8, 186, 10.3390/antiox8060186 Fu, 2013, Antioxidant and anti-inflammatory activities of six flavonoids separated from licorice, Food Chem, 141, 1063, 10.1016/j.foodchem.2013.03.089 Fukuchi, 2016, Antiviral and antitumor activity of licorice root extracts, In Vivo (Brooklyn), 30, 777, 10.21873/invivo.10994 Gajewski, 2021, Potential of herbal products in prevention and treatment of COVID-19. Literature review, Biomed. Pharmacother., 143, 10.1016/j.biopha.2021.112150 Gao, 2015, Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats, Front. Pharmacol., 6, 215, 10.3389/fphar.2015.00215 Ghannad, 2014, The Effect of aqueous extract of Glycyrrhiza glabra on herpes simplex virus 1, Jundishapur J. Microbiol., 7, e11616 Grienke, 2014, Computer-guided approach to access the anti-influenza activity of licorice constituents, J. Nat. Prod., 77, 563, 10.1021/np400817j Guo, 2015, Promotion of regulatory T cell induction by immunomodulatory herbal medicine licorice and its two constituents, Sci. Rep., 5, 14046, 10.1038/srep14046 Han, 2017, Anti-allergic activity of glycyrrhizic acid on IgE-mediated allergic reaction by regulation of allergy-related immune cells, Sci. Rep., 7, 7222, 10.1038/s41598-017-07833-1 Hasan, 2021, Phytochemistry, pharmacological activity, and potential health benefits of Glycyrrhiza glabra, Heliyon, 7, e07240, 10.1016/j.heliyon.2021.e07240 Hatano, 1988, Anti-human immunodeficiency virus phenolics from licorice, Chem. Pharm. Bull (Tokyo)., 36, 2286, 10.1248/cpb.36.2286 Hocaoglu, 2011, Glycyrrhizin and long-term histopathologic changes in a murine model of asthma, Curr. Ther. Res. Clin. Exp., 72, 250, 10.1016/j.curtheres.2011.11.002 Honarmand, 2016, The efficacy of different doses of liquorice gargling for attenuating postoperative sore throat and cough after tracheal intubation, Eur. J. Anaesthesiol., 33, 595, 10.1097/EJA.0000000000000400 Honda, 2014, Isoliquiritigenin is a potent inhibitor of NLRP3 inflammasome activation and diet-induced adipose tissue inflammation, J. Leukoc. Biol., 96, 1087, 10.1189/jlb.3A0114-005RR Hong, 2009, Effects of Glycyrrhiza glabra polysaccharides on immune and antioxidant activities in high-fat mice, Int. J. Biol. Macromol., 45, 61, 10.1016/j.ijbiomac.2009.04.001 Hosseini, 2020, Association analysis and molecular tagging of phytochemicals in the endangered medicinal plant licorice (Glycyrrhiza glabra L.), Phytochemistry, 183 Hosseinzadeh, 2015, Pharmacological effects of Glycyrrhiza spp. and its bioactive constituents: update and review, Phytother. Res., 29, 1868, 10.1002/ptr.5487 Hu, 2021, He-Jie-Shen-Shi decoction as an adjuvant therapy on severe coronavirus disease 2019: a retrospective cohort and potential mechanistic study, Front. Pharmacol., 12, 10.3389/fphar.2021.700498 Huaccho-Rojas, 2020, Review of antiviral and immunomodulatory effects of herbal medicine with reference to pandemic COVID-19, Arch. Venez. Farmacol. Ter., 39, 795 Huan, 2020, Study on antiviral activities of glycyrrhizin, Int. J. Biomed. Eng. Clin. Sci., 6, 68, 10.11648/j.ijbecs.20200604.11 Huan, 2021, Research progress on the antiviral activity of glycyrrhizin and its derivatives in liquorice, Front. Pharmacol., 12, 10.3389/fphar.2021.680674 Huang, 2017, Licochalcone A prevents the loss of dopaminergic neurons by inhibiting microglial activation in lipopolysaccharide (LPS)-induced parkinson's disease models, Int. J. Mol. Sci., 18, 2043, 10.3390/ijms18102043 Ibrahim, 2021, Biologically guided isolation and ADMET profile of new factor Xa inhibitors from Glycyrrhiza glabra roots using in vitro and in silico approaches, RSC Adv, 11, 9995, 10.1039/D1RA00359C Idrees, 2021, Effect of the phytochemical agents against the SARS-CoV and some of them selected for application to COVID-19: a mini-review, Curr. Pharm. Biotechnol., 22, 444, 10.2174/1389201021666200703201458 Ishimaru, 2019, Placebo on sore throat associated with acute upper respiratory tract infection: a randomized controlled trial, Intern. Med., 58, 2459, 10.2169/internalmedicine.2748-19 Jahromi, 2019, Comparing the effects of Glycyrrhiza glabra root extract, a cyclooxygenase-2 inhibitor (celecoxib) and a gonadotropin-releasing hormone analog (diphereline) in a rat model of endometriosis, Int. J. Fertil. Steril., 13, 45 Jalali, 2021, A pharmacology-based comprehensive review on medicinal plants and phytoactive constituents possibly effective in the management of COVID-19, Phytother. Res, 35, 1925, 10.1002/ptr.6936 Javadi, 2017, Medicinal plants for the treatment of asthma: a traditional persian medicine perspective, Curr. Pharm. Des., 23, 1623, 10.2174/1381612822666161021143332 Javid, 2019, Short-course administration of a traditional herbal mixture ameliorates asthma symptoms of the common cold in children, Avicenna J. Phytomed., 9, 126 Jayaprakasam, 2013, Constituents of the anti-asthma herbal formula ASHMI (TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro, J. Integr. Med., 11, 195, 10.3736/jintegrmed2013029 Jeong, 2015, Traditional herbal formula Jakyakgamcho-tang (Paeonia lactiflora and Glycyrrhiza uralensis) impairs inflammatory chemokine production by inhibiting activation of STAT1 and NF-kappaB in HaCaT cells, Phytomedicine, 22, 326, 10.1016/j.phymed.2014.12.002 Jezova, 2020, Food enrichment with Glycyrrhiza glabra extract suppresses ACE2 mRNA and protein expression in rats-possible implications for COVID-19, Nutrients, 13, 2321, 10.3390/nu13072321 Jiang, 2020, An “essential herbal medicine”-licorice: a review of phytochemicals and its effects in combination preparations, J. Ethnopharmacol., 249, 10.1016/j.jep.2019.112439 Jitsuiki, 2020, Successful treatment of elderly male with COVID-19 infection with severe acute respiratory distress syndrome using multimodal therapy, including immune modulation therapy, Cureus, 12, e12402 Kao, 2014, Bioactivity and potential health benefits of licorice, J. Agric. Food Chem., 62, 542, 10.1021/jf404939f Katayama, 2011, Effect of dietary addition of seaweed and licorice on the immune performance of pigs, Anim. Sci. J., 82, 274, 10.1111/j.1740-0929.2010.00826.x Kaur, 2017, Immunopotentiating significance of conventionally used plant adaptogens as modulators in biochemical and molecular signalling pathways in cell mediated processes, Biomed. Pharmacother., 95, 1815, 10.1016/j.biopha.2017.09.081 Kaur, 2013, Glycyrrhiza glabra: a phytopharmacological review, Int. J. Pharm. Sci. Res., 4, 2470 Khan, 2021, Therapeutic potential of medicinal plants against COVID-19: the role of antiviral medicinal metabolites, Biocatal. Agric. Biotechnol., 31, 10.1016/j.bcab.2020.101890 Kim, 2006, Anti-inflammatory effect of roasted licorice extracts on lipopolysaccharide-induced inflammatory responses in murine macrophages, Biochem. Biophys. Res. Commun., 345, 1215, 10.1016/j.bbrc.2006.05.035 Kim, 2020, Herbal combinational medication of Glycyrrhiza glabra, agastache rugosa containing Glycyrrhizic acid, tilianin inhibits neutrophilic lung inflammation by affecting CXCL2, interleukin-17/STAT3 signal pathways in a murine model of COPD, Nutrients, 12, 926, 10.3390/nu12040926 Kim, 2014, The antiinflammatory mechanism of Igongsan in mouse peritoneal macrophages via suppression of NF-κB/Caspase-1 activation, Phytother. Res., 28, 736, 10.1002/ptr.5058 Kinoshita, 2021, 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., 33, 3099, 10.1007/s40520-020-01513-3 Kuang, 2018, Antitussive and expectorant activities of licorice and its major compounds, Bioorg. Med. Chem., 26, 278, 10.1016/j.bmc.2017.11.046 Kumar, 2013, PA02. 14. A review on immunomodulator activity of Yashtimadhu (Glycyrrhiza glabra), Anc. Sci. Life., 32, S59, 10.4103/0257-7941.123878 Kwon, 2020, A review of the pharmacological efficacy and safety of Licorice root from corroborative clinical trial findings, J. Med. Food., 23, 12, 10.1089/jmf.2019.4459 Langer, 2016, Glycyrrhetinic acid and its derivatives in infectious diseases, Curr. Issues Pharm. Medical Sci., 29, 118, 10.1515/cipms-2016-0024 Lee, 2013, Mechanisms by which licochalcone exhibits potent anti-inflammatory properties: studies with phorbol ester-treated mouse skin and lipopolysaccharide-stimulated murine macrophages, Int. J. Mol. Sci., 14, 10926, 10.3390/ijms140610926 Lee, 2019, Effects of glycyrrhizin on lipopolysaccharide-induced acute lung injury in a mouse model, J. Thorac Dis., 11, 1287, 10.21037/jtd.2019.04.14 Li, 2015, Glycyrrhiza glabra (L.) extract inhibits LPS-induced inflammation in RAW macrophages, J. Nutr. Sci. Vitaminol (Tokyo)., 61, 375, 10.3177/jnsv.61.375 Li, 2021, Glycyrrhizic acid inhibits SARS-CoV-2 infection by blocking spike protein-mediated cell attachment, Molecules, 26, 6090, 10.3390/molecules26206090 Li, 2021, Chemical composition and pharmacological mechanism of ephedra-glycyrrhiza drug pair against coronavirus disease 2019 (COVID-19), Aging (Albany NY), 13, 4811, 10.18632/aging.202622 Li, 2021, Potential effect of Maxing Shigan decoction against coronavirus disease 2019 (COVID-19) revealed by network pharmacology and experimental verification, J. Ethnopharmacol., 271, 10.1016/j.jep.2021.113854 Liana, 2021, Leveraging knowledge of Asian herbal medicine and its active compounds as COVID-19 treatment and prevention, J. Nat. Med., 8, 1 Lin, 2003, Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus replication in vitro, Antiviral Res, 59, 41, 10.1016/S0166-3542(03)00030-5 Liu, 2008, Isoliquiritigenin, a flavonoid from licorice, relaxes guinea-pig tracheal smooth muscle in vitro and in vivo: role of cGMP/PKG pathway, Eur. J. Pharmacol., 587, 257, 10.1016/j.ejphar.2008.03.015 Liu, 2020, Liquiritin, a novel inhibitor of TRPV1 and TRPA1, protects against LPS-induced acute lung injury, Cell Calcium, 88, 10.1016/j.ceca.2020.102198 Liu, 2014, Effects of glycyrrhizin acid and licorice flavonoids on LPS-induced cytokines expression in macrophage, Zhongguo Zhong Yao Za Zhi, 39, 3841 Lu, 2008, Ri-mediated transformation of Glycyrrhiza uralensis with a squalene synthase gene (GuSQS1) for production of glycyrrhizin, Plant Mol. Biol. Rep., 26, 1, 10.1007/s11105-008-0018-7 Ma, 2013, 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, J. Ethnopharmacol., 148, 755, 10.1016/j.jep.2013.04.021 Ma, 2013, 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, J. Ethnopharmacol., 148, 755, 10.1016/j.jep.2013.04.021 Malekmohammad, 2021, Mechanistic aspects of medicinal plants and secondary metabolites against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Curr. Pharm. Des., 27, 3996, 10.2174/1381612827666210705160130 Mamedov, 2019, Phytochemical constituents and pharmacological effects of licorice: a review, Plant and Human Health (Springer, Cham), 3, 1 Man, 2020, Licorice ameliorates cisplatin-induced hepatotoxicity through antiapoptosis, antioxidative stress, anti-inflammation, and acceleration of metabolism, Front. Pharmacol., 11, 10.3389/fphar.2020.563750 Marotti, 2021, Evaluation of licorice (Glycyrrhiza glabra L.) as a novel microgreen from the anti-inflammatory potential of polyphenols, AIMS Agric. Food, 6, 1, 10.3934/agrfood.2021001 Mazumder, 2012, Evaluation of immunomodulatory activity of Glycyrrhiza glabra L roots in combination with zinc, Asian Pac. J. Trop. Biomed., 2, S15, 10.1016/S2221-1691(12)60122-1 Mehrbod, 2021, Potential antiviral effects of some native Iranian medicinal plants extracts and fractions against influenza A virus, BMC Complement. Med. Ther., 21, 246, 10.1186/s12906-021-03423-x Menegazzi, 2008, Glycyrrhizin attenuates the development of carrageenan-induced lung injury in mice, Pharmacol. Res., 58, 22, 10.1016/j.phrs.2008.05.012 Merarchi, 2021, Natural products and phytochemicals as potential anti-SARS-CoV-2 drugs, Phytother. Res, 35, 5384, 10.1002/ptr.7151 Michaelis, 2011, Glycyrrhizin exerts antioxidative effects in H5N1 Influenza A virus-infected cells and inhibits virus replication and pro-inflammatory gene expression, PLoS ONE, 6, e19705, 10.1371/journal.pone.0019705 Moradi, 2014, Performance and some immunological parameter responses of broiler chickens to Licorice (Glycyrrhiza glabra) extract administration in the drinking water, Annu. Res. Rev. Biol., 4, 675, 10.9734/ARRB/2014/5277 Murck, 2020, Symptomatic protective action of Glycyrrhizin (Licorice) in COVID-19 infection?, Front. Immunol., 11, 1239, 10.3389/fimmu.2020.01239 Nabeshima, 2012, A randomized, controlled trial comparing traditional herbal medicine and neuraminidase inhibitors in the treatment of seasonal influenza, J. Infect. Chemother., 18, 534, 10.1007/s10156-012-0378-7 Nasiri, 2020, Rheological behavior of Glycyrrhiza glabra (Licorice) extract as a function of concentration and temperature: a critical reappraisal, Foods, 9, 1872, 10.3390/foods9121872 Nasiriasl, 2007, Review of antiviral effects of Glycyrrhiza glabra L. and its active component, glycyrrhizin, J. Med. Plants, 6, 1 Nazari, 2017, Toxicological effects of Glycyrrhiza glabra L. (Licorice): a review, Phytother. Res., 31, 1635, 10.1002/ptr.5893 Ng, S.L., Khaw, K.Y., Ong, Y.S., Goh, H.P., Kifli, N., Teh, S.P., Ming, L.C., Kotra, V., Goh, B.H., 2021. Licorice: a potential herb in overcoming SARS-CoV-2 infections. J. Evid. Based Integr. Med. doi: 10.1177/2515690X21996662. Nirmala, 2011, Anti-inflammatory and anti-bacterial activities of Glycyrrhiza glabra (L.), J. Agric. Technol., 7, 815 Nose, 1998, Activation of macrophages by crude polysaccharide fractions obtained from shoots of Glycyrrhiza glabra and hairy roots of Glycyrrhiza uralensis in vitro, Biol. Pharm. Bull., 21, 1110, 10.1248/bpb.21.1110 Olukoga, 2000, Liquorice and its health implications, J. R. Soc. Promot. Health., 120, 83, 10.1177/146642400012000203 Omer, 2014, Comparative study to evaluate the anti-viral efficacy of Glycyrrhiza glabra extract and ribavirin against the Newcastle disease virus, Pharmacognosy Res, 6, 6, 10.4103/0974-8490.122911 Pandey, 2017, A review on constituents, pharmacological activities and medicinal uses of Glycyrrhiza glabra, Univers. J. Pharm. Res., 2, 26, 10.22270/ujpr.v2i2.RW2 Panossian, 2020, The Role of adaptogens in prophylaxis and treatment of Viral Respiratory Infections, Pharmaceuticals (Basel), 13, 236, 10.3390/ph13090236 Parizipour, 2020, Investigation of antiviral potential of licorice (Glycyrrhiza glabra L.) crude extract against tobacco mosaic virus, J. Anim. Plant Sci, 30, 107 Pastorino, 2018, Liquorice (Glycyrrhiza glabra): a phytochemical and pharmacological review, Phytother. Res., 32, 2323, 10.1002/ptr.6178 Putalun, 2011, Enhanced glycyrrhizin production in Glycyrrhiza inflata hairy roots cultures using elicitation, Planta Med., 77, PB14, 10.1055/s-0031-1282268 Racková, 2007, Mechanism of anti-inflammatory action of liquorice extract and glycyrrhizin, Nat. Prod. Res., 21, 1234, 10.1080/14786410701371280 Rangnekar, 2020, Safety and efficacy of herbal extracts to restore respiratory health and improve innate immunity in COVID-19 positive patients with mild to moderate severity: a structured summary of a study protocol for a randomized controlled trial, Trials, 21, 943, 10.1186/s13063-020-04906-x Rani, 2021, Glycyrrhiza glabra: an insight to nanomedicine, J. Nanosci. Nanotechnol., 21, 3367, 10.1166/jnn.2021.19007 Rehman, 2020, Preclinical evidence for the pharmacological actions of glycyrrhizic acid: a comprehensive review, Curr. Drug Metab., 21, 436, 10.2174/1389200221666200620204914 Ren, 1988, Pharmacological research on the effect of licorice, J. Tradit. Chin. Med., 8, 307 Revers, 1956, Clinical and pharmacological investigations on extract of licorice, Acta Med. Scand. Suppl., 312, 749, 10.1111/j.0954-6820.1956.tb17084.x Richard, 2021, Exploring the pivotal immunomodulatory and anti-inflammatory potentials of glycyrrhizic and glycyrrhetinic Acids, Mediators Inflamm., 6699560, 1, 10.1155/2021/6699560 Safa, 2020, Effects of Licorice on clinical symptoms and laboratory signs in moderately ill patients with pneumonia from COVID-19: a structured summary of a study protocol for a randomized controlled trial, Trials, 21, 790, 10.1186/s13063-020-04706-3 Saha, 2011, Structural features and in vivo antitussive activity of the water extracted polymer from Glycyrrhiza glabra, Int. J. Biol. Macromol., 48, 634, 10.1016/j.ijbiomac.2011.02.003 Samareh Fekri, 2021, The effects of methanolic extract of Glycyrrhiza glabra on the prevention and treatment of bleomycin-induced pulmonary fibrosis in rat: experimental study, Drug Chem. Toxicol., 44, 365, 10.1080/01480545.2019.1606232 Saxena, 2005, Glycyrrhiza glabra: medicine Over Millennium, Nat. Prod. Radiance, 4, 358 Schröfelbauer, 2009, Glycyrrhizin, the main active compound in liquorice, attenuates pro-inflammatory responses by interfering with membrane-dependent receptor signalling, Biochem. J., 421, 473, 10.1042/BJ20082416 Seki, 2008, Licorice beta-amyrin 11-oxidase, a cytochrome P450 with a key role in the biosynthesis of the triterpene sweetener glycyrrhizin, Proc. Natl. Acad. Sci. USA., 105, 14204, 10.1073/pnas.0803876105 Seki, 2011, Triterpene functional genomics in licorice for identification of CYP72A154 involved in the biosynthesis of glycyrrhizin, Plant Cell, 23, 4112, 10.1105/tpc.110.082685 Shabani, 2009, Glycyrrhizin production by in vitro cultured Glycyrrhiza glabra elicited by methyl Jasmonate and salicylic acid, Russ. J. Plant Physiol., 56, 621, 10.1134/S1021443709050069 Shakhsi-Niaei, 2021, In silico comparison of separate or combinatorial effects of potential inhibitors of the SARS-CoV-2 binding site of ACE2, Iran J. Public Health., 50, 1028 Sharifi-Rad, 2021, Glycyrrhiza genus: enlightening phytochemical components for pharmacological and health-promoting abilities, Oxid. Med. Cell. Longev., 7571132, 1 Sharma, 2018, Glycyrrhiza glabra: chemistry and pharmacological activity. Sweeteners, 87, 10.1007/978-3-319-27027-2_21 Sheikhi, 2021, Immunotherapeutic Effects of Glycyrrhiza glabra and Glycyrrhizic Acid on Leishmania major Infected BALB/C Mice, Parasite Immunol, 24, e12879 Shitole, 2019, Study of potential antitussive activity of Glycyrrhiza glabra granules by using a cough model induced by Sulphur dioxide gas in mice, Asian J. Pharm. Clin. Res., 12, 262, 10.22159/ajpcr.2019.v12i10.33967 Silveira, 2020, COVID-19: is there evidence for the use of herbal medicines as adjuvant symptomatic therapy?, Front. Pharmacol, 11, 10.3389/fphar.2020.581840 Sinha, 2021, Potential leads from liquorice against SARS-CoV-2 main protease using molecular docking simulation studies, Comb. Chem. High Throughput Screen, 24, 591, 10.2174/1386207323999200817103148 Sinha, 2021, Identification of bioactive compounds from Glycyrrhiza glabra as possible inhibitor of SARS-CoV-2 spike glycoprotein and non-structural protein-15: a pharmacoinformatics study, J. Biomol. Struct. Dyn., 39, 4686, 10.1080/07391102.2020.1779132 Siracusa, 2011, Phyto-complexes from liquorice (Glycyrrhiza glabra L.) leaves - chemical characterization and evaluation of their antioxidant, anti-genotoxic, and anti-inflammatory activity, Fitoterapia, 82, 546, 10.1016/j.fitote.2011.01.009 Soufy, 2012, Antiviral and immune stimulant activities of glycyrrhizin against duck hepatitis virus, Afr. J. Tradit. Complement. Altern. Med., 9, 389, 10.4314/ajtcam.v9i3.14 Srivastava, 2019, Elicitation enhanced the yield of glycyrrhizin and antioxidant activities in hairy root cultures of Glycyrrhiza glabra L, J. Plant Growth Regul., 38, 373, 10.1007/s00344-018-9847-2 Srivastava, 2020, Molecular docking and ADMET study of bioactive compounds of Glycyrrhiza glabra against main protease of SARS-CoV2, Mater. Today Proc, 14 Sun, 2021, Anti-inflammatory effect of herbal traditional medicine extract on molecular regulation in allergic asthma, Allergol. Select, 5, 148, 10.5414/ALS400545 Sun, 2019, Research progress of glycyrrhizic acid on antiviral activity, Mini. Rev. Med. Chem., 19, 826, 10.2174/1389557519666190119111125 Taniguchi, 2000, Pharmacological effects of urinary products obtained after treatment with Saiboku-to, a herbal medicine for bronchial asthma, on type IV allergic reaction, Planta Med., 66, 607, 10.1055/s-2000-8626 Tiwari, 2018, Herbal immunomodulators - a remedial panacea for designing and developing effective drugs and medicines: current scenario and future prospects, Curr. Drug Metab., 19, 264, 10.2174/1389200219666180129125436 Trombetta, 2014, Selective COX-2 inhibitory properties of dihydrostilbenes from liquorice leaves–in vitro assays and structure/activity relationship study, Nat. Prod. Commun., 9, 1761 Tsai, 2021, GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2, Biomed. Pharmacother., 142, 10.1016/j.biopha.2021.112011 van de Sand, 2021, Glycyrrhizin effectively inhibits SARS-CoV-2 replication by inhibiting the viral main protease, Viruses, 13, 609, 10.3390/v13040609 Wagner, 2002, Immunological studies of Revitonil, a phytopharmaceutical containing Echinacea purpurea and Glycyrrhiza glabra root extract, Phytomedicine, 9, 390, 10.1078/09447110260571616 Wahab, 2021, Pharmacological Efficacy and Safety of Glycyrrhiza glabra in the treatment of respiratory tract infections, Mini Rev. Med. Chem., 10.2174/1389557521666210927153001 Wang, 2020, A comprehensive review for phytochemical, pharmacological, and biosynthesis studies on Glycyrrhiza spp, Am. J. Chin. Med., 48, 17, 10.1142/S0192415X20500020 Wang, 2011, Glycyrrhizic acid and 18β-glycyrrhetinic acid modulate lipopolysaccharide-induced inflammatory response by suppression of NF-κB through PI3K p110δ and p110γ inhibitions, J. Agric. Food Chem., 59, 7726, 10.1021/jf2013265 Wang, 2015, The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb, Acta Pharm. Sin. B, 5, 310, 10.1016/j.apsb.2015.05.005 Wang, 2021, Interaction of natural compounds in licorice and turmeric with HIV-NCp7 zinc finger domain: potential relevance to the mechanism of antiviral activity, Molecules, 26, 3563, 10.3390/molecules26123563 Wang, 2006, The anti-respiratory syncytial virus effect of active compound of Glycyrrhiza GD4 in vitro, Zhong Yao Cai, 29, 692 Watanabe, 2016, Isoliquiritigenin attenuates adipose tissue inflammation in vitro and adipose tissue fibrosis through inhibition of innate immune responses in mice, Sci. Rep., 6, 23097, 10.1038/srep23097 Wolkerstorfer, 2009, Glycyrrhizin inhibits influenza A virus uptake into the cell, Antiviral. Res., 83, 171, 10.1016/j.antiviral.2009.04.012 Wongwicha, 2011, Methyl jasmonate elicitation enhances glycyrrhizin production in Glycyrrhiza inflata hairy roots cultures, Z. Naturforsch. C. J. Biosci., 66, 423, 10.1515/znc-2011-7-815 Wu, 2017, Licocoumarone isolated from Glycyrrhiza uralensis selectively alters LPS-induced inflammatory responses in RAW 264.7 macrophages, Eur. J. Pharmacol., 801, 46, 10.1016/j.ejphar.2017.02.049 Xie, 2009, Inhibitory effects of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice, Int. Immunopharmacol., 9, 194, 10.1016/j.intimp.2008.11.004 Yang, 2020, Food as medicine: a possible preventive measure against coronavirus disease (COVID-19), Phytother. Res., 24, 3124, 10.1002/ptr.6770 Yang, 2018, Licochalcone A attenuates acne symptoms mediated by suppression of NLRP3 inflammasome, Phytother. Res., 32, 2551, 10.1002/ptr.6195 Yang, 2015, The pharmacological activities of Licorice, Planta Med, 81, 1654, 10.1055/s-0035-1557893 Yang, 2017, The anti-inflammatory activity of licorice, a widely used Chinese herb, Pharm. Biol., 55, 5, 10.1080/13880209.2016.1225775 Yu, 2015, Anti-inflammatory activities of licorice extract and its active compounds, glycyrrhizic acid, liquiritin, and liquiritigenin, in BV2 cells and mice liver, Molecules, 20, 13041, 10.3390/molecules200713041 Yu, 2017, The Effect of Chinese herbal medicine formula mKG on allergic asthma by regulating lung and pasma metabolic alternations, Int. J. Mol. Sci., 18, 602, 10.3390/ijms18030602 Yu, 2019, Multi‑pathway integrated adjustment mechanism of licorice flavonoids presenting anti‑inflammatory activity, Oncol. Lett., 18, 4956 Yuan, 2021, Licochalcone A inhibits interferon-gamma-induced programmed death-ligand 1 in lung cancer cells, Phytomedicine, 80, 10.1016/j.phymed.2020.153394 Zhang, 2017, Synergistic protection of Schizandrin B and Glycyrrhizic acid against bleomycin-induced pulmonary fibrosis by inhibiting TGF-β1/Smad2 pathways and overexpression of NOX4, Int. Immunopharmacol., 48, 67, 10.1016/j.intimp.2017.04.024 Zhao, 2018, The intervention effect of licorice in d-galactose induced aging rats by regulating the taurine metabolic pathway, Food Funct, 9, 4814, 10.1039/C8FO00740C Zhong, 2020, Potential targets for treatment of coronavirus disease2019 (COVID-19): a review of Qing-Fei-Pai-Du-Tang and its major herbs, Am. J. Chin. Med., 48, 1051, 10.1142/S0192415X20500512