Recent Advances in the Pharmacological Activities of Glycyrrhizin, Glycyrrhetinic Acid, and Their Analogs

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Akutagawa K, Fujita T, Ouhara K, Takemura T, Tari M, Kajiya M, Matsuda S, Kuramitsu S, Mizuno N, Shiba H, Kurihara H (2019) Glycyrrhizic acid suppresses inflammation and reduces the increased glucose levels induced by the combination of Porphyromonas gulae and ligature placement in diabetic model mice. Int Immunopharmacol 68:30–38. https://doi.org/10.1016/j.intimp.2018.12.045

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Azmoudeh F, Nazeri N (2023) Nanocurcumin: its applications in preventive, restorative, and regenerative dentistry. Rev Bras Farmacogn. https://doi.org/10.1007/s43450-023-00427-1

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Bai M, Yao GD, Ren Q, Li Q, Liu QB, Zhang Y, Wang XB, Huang XX, Song SJ (2018) Triterpenoid saponins and flavonoids from licorice residues with anti-inflammatory activity. Ind Crops Prod 125:50–58. https://doi.org/10.1016/j.indcrop.2018.08.075

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Balkrishna A, Sharma P, Joshi M, Srivastava J, Varshney A (2021) Development and validation of a rapid high-performance thin-layer chromatographic method for quantification of gallic acid, cinnamic acid, piperine, eugenol, and glycyrrhizin in Divya-Swasari-Vati, an Ayurvedic medicine for respiratory ailments. J Sep Sci 44:3146–3157. https://doi.org/10.1002/jssc.202100096

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Baltina LA, Hour MJ, Liu YC, Chang YS, Huang SH, Lai HC, Kondratenko RM, Petrova SF, Yunusov MS, Lin CW (2021a) Antiviral activity of glycyrrhizic acid conjugates with amino acid esters against Zika virus. Virus Res 294:198290. https://doi.org/10.1016/j.virusres.2020.198290

Baltina LA, Lai HC, Liu YC, Huang SH, Hour MJ, Baltina LA, Nugumanov TR, Borisevich SS, Khalilov LM, Petrova SF, Khursan SL, Lin CW (2021b) Glycyrrhetinic acid derivatives as Zika virus inhibitors: synthesis and antiviral activity in vitro. Bioorg Med Chem 41:116204. https://doi.org/10.1016/j.bmc.2021.116204

Baltina LA, Sapozhnikova TA, Gabdrakhmanova SF, Makara NS, Khisamutdinova RY, Baltina LA Jr, Petrova SF, Saifullina DR, Kondratenko RM (2021c) Hypoglycemic activity of glycyrrhizic acid and some of its derivatives in the alloxan diabetes model in rats. Pharm Chem J 55:340–344. https://doi.org/10.1007/s11094-021-02424-x

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Ban JY, Park HK, Kim SK (2020) Effect of glycyrrhizic acid on scopolamine-induced cognitive impairment in mice. Int Neurourol J 24:S48-55. https://doi.org/10.5213/inj.2040154.077

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Bian M, Zhen D, Shen QK, Du HH, Ma QQ, Quan ZS (2021) Structurally modified glycyrrhetinic acid derivatives as anti-inflammatory agents. Bioorg Chem 107:104598. https://doi.org/10.1016/j.bioorg.2020.104598

Carod-Artal FJ (2018) Neurological complications of Zika virus infection. Expert Rev Anti-Infect Ther 16:399–410. https://doi.org/10.1080/14787210.2018.1466702

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Chauhan S, Gulati N, Nagaich U (2018) Glycyrrhizic acid: extraction, screening and evaluation of anti–inflammatory property. Ars Pharm 59:61–67. https://doi.org/10.30827/ars.v59i2.7513

Chen K, Yang R, Shen FQ, Zhu HL (2020) Advances in pharmacological activities and mechanisms of glycyrrhizic acid. Curr Med Chem 27:6219–6243. https://doi.org/10.2174/0929867325666191011115407

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Cheng M, Ding L, Kan H, Zhang H, Jiang B, Sun Y, Cao S, Li W, Koike K, Qiu F (2019) Isolation, structural elucidation and in vitro hepatoprotective activity of flavonoids from Glycyrrhiza uralensis. J Nat Med 73:847–854. https://doi.org/10.1007/s11418-019-01329-0

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Cheng M, Zhang J, Yang L, Shen S, Li P, Yao S, Wei W, Guo DA (2021) Recent advances in chemical analysis of licorice (Gan-Cao). Fitoterapia 149:104803. https://doi.org/10.1016/j.fitote.2020.104803

Diomede L, Beeg M, Gamba A, Fumagalli O, Gobbi M, Salmona M (2021) Can antiviral activity of licorice help fight COVID-19 infection? Biomolecules 11:855. https://doi.org/10.3390/biom11060855

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Elebeedy D, Elkhatib WF, Kandeil A, Ghanem A, Kutkat O, Alnajjar R, Saleh MA, Abd El Maksoud AI, Badawy I, Al-Karmalawy AA (2021) Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational and in vitro insights. RSC Adv 11:29267–29286. https://doi.org/10.1039/D1RA05268C

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Esmaeili H, Karami A, Hadian J, Saharkhiz MJ, Ebrahimi SN (2019) Variation in the phytochemical contents and antioxidant activity of Glycyrrhiza glabra populations collected in Iran. Ind Crops Prod 137:248–259. https://doi.org/10.1016/j.indcrop.2019.05.034

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Farmanzadeh D, Tabari L (2017) Glycyrrhizic acid and its salts as antioxidant; a computational investigation. J Indian Chem Soc 94:261–267

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Fathima F, Rajeshkumar S (2021) In vitro anti-diabetic activity of Glycyrrhiza glabra ethanolic extract. Ann Romanian Soc Cell Biol 25:2497–2502

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Glavač NK, Kreft S (2012) Excretion profile of glycyrrhizin metabolite in human urine. Food Chem 131:305–308. https://doi.org/10.1016/j.foodchem.2011.08.081

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Graebin CS (2018) The pharmacological activities of glycyrrhizinic acid (“glycyrrhizin”) and glycyrrhetinic acid. In: Mérillon JM, Ramawat K (eds) Sweeteners. Reference Series in Phytochemistry. Springer, Cham, pp 245–261. https://doi.org/10.1007/978-3-319-27027-2_15

Hasan MK, Ara I, Mondal MSA, Kabir Y (2021) Phytochemistry, pharmacological activity, and potential health benefits of Glycyrrhiza glabra. Heliyon 7:e07240. https://doi.org/10.1016/j.heliyon.2021.e07240

Huan C, Xu Y, Zhang W, Guo T, Pan H, Gao S (2021) Research progress on the antiviral activity of glycyrrhizin and its derivatives in liquorice. Front Pharmacol 12:680674. https://doi.org/10.3389/fphar.2021.680674

Huo X, Meng X, Zhang J, Zhao Y (2020) Hepatoprotective effect of different combinations of 18α-and 18β-glycyrrhizic acid against CCl4-induced liver injury in rats. Biomed. Pharmacother 122:109354. https://doi.org/10.1016/j.biopha.2019.109354

Hussain H, Green IR, Shamraiz U, Saleem M, Badshah A, Abbas G, Rehman UN, Irshad M (2018) Therapeutic potential of glycyrrhetinic acids: a patent review (2010–2017). Expert Opin Ther Pat 28:383–398. https://doi.org/10.1080/13543776.2018.1455828

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Icer MA, Sanlier N, Sanlier N (2017) A review: pharmacological effects of licorice (Glycyrrhiza glabra) on human health. Int J Basic Clin Pharmacol 6:12–26

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Jin L, Dai L, Ji M, Wang H (2019) Mitochondria-targeted triphenylphosphonium conjugated glycyrrhetinic acid derivatives as potent anticancer drugs. Bioorg Chem 85:179–190. https://doi.org/10.1016/j.bioorg.2018.12.036

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Kowalska A, Kalinowska-Lis U (2019) 18β-Glycyrrhetinic acid: its core biological properties and dermatological applications. Int J Cosmet Sci 41:325–331. https://doi.org/10.1111/ics.12548

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Kumar A, Archo S, Singh CP, Naikoo SH, Singh B, Kaur S, Tasduq SA (2022) Photoprotective effect of 18β-glycyrrhetinic acid derivatives against ultra violet (UV)-B-induced skin aging. Bioorganic Med Chem Lett 76:128984. https://doi.org/10.1016/j.bmcl.2022.128984

Kwon YJ, Son DH, Chung TH, Lee YJ (2020) A review of the pharmacological efficacy and safety of licorice root from corroborative clinical trial findings. J Med Food 23:12–20. https://doi.org/10.1089/jmf.2019.4459

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Lee JC, Seksama LH, Park CH, Kim CS (2023) Enhancing the anti-bacterial activity of nanofibrous polyurethane membranes by incorporating glycyrrhizic acid-conjugated β-cyclodextrin. Mater Lett 338:134030. https://doi.org/10.1016/j.matlet.2023.134030

Lin Y, Kuang Y, Li K, Wang S, Ji S, Chen K, Song W, Qiao X, Ye M (2017) Nrf2 activators from Glycyrrhiza inflata and their hepatoprotective activities against CCl4-induced liver injury in mice. Bioorg Med Chem 25:5522–5530. https://doi.org/10.1016/j.bmc.2017.08.018

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Maestrini M, Molento MB, Forzan M, Perrucci S (2021) In vitro anthelmintic activity of an aqueous extract of Glycyrrhiza glabra and of glycyrrhetinic acid against gastrointestinal nematodes of small ruminants. Parasite 28:64. https://doi.org/10.1051/parasite/2021060

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Meteleva ES, Chistyachenko YS, Suntsova LP, Khvostov MV, Polyakov NE, Selyutina OY, Tolstikova TG, Frolova TS, Mordvinov VA, Dushkin AV, Lyakhov NZ (2019) Disodium salt of glycyrrhizic acid–a novel supramolecular delivery system for anthelmintic drug praziquantel. J Drug Deliv Sci Technol 50:66–77. https://doi.org/10.1016/j.jddst.2019.01.014

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Mittal A, Kakkar R (2020) The effect of solvent polarity on the antioxidant potential of echinatin, a retrochalcone, towards various ROS: a DFT thermodynamic study. Free Radic Res 54:777–786. https://doi.org/10.1080/10715762.2020.1849670

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Mittal A, Devi SP, Kakkar R (2020) A DFT study of the conformational and electronic properties of echinatin, a retrochalcone, and its anion in the gas phase and aqueous solution. Struct Chem 31:2513–2524. https://doi.org/10.1007/s11224-020-01598-6

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Mittal A, Vashistha VK, Das DK (2022) Recent advances in the antioxidant activity and mechanisms of chalcone derivatives: a computational review. Free Radic Res 56:378–397. https://doi.org/10.1080/10715762.2022.2120396

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Mittal A, Vashistha VK, Das DK (2023) Free radical scavenging activity of gallic acid toward various reactive oxygen, nitrogen, and sulfur species: a DFT approach. Free Radic Res 57:81–90. https://doi.org/10.1080/10715762.2023.2197556

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Mittal A, Kakkar R (2021a) Synthetic methods and biological applications of retrochalcones isolated from the root of Glycyrrhiza species: a review. Results Chem 3:100216. https://doi.org/10.1016/j.rechem.2021.100216

Mittal A, Kakkar R (2021b) A theoretical assessment of the structural and electronic features of some retrochalcones. Int J Quantum Chem 121:e26797. https://doi.org/10.1002/qua.26797

Mittal A, Kakkar R (2021c) The antioxidant potential of retrochalcones isolated from liquorice root: a comparative DFT study. Phytochemistry 192:112964. https://doi.org/10.1016/j.phytochem.2021.112964

Mohammed EAH, Peng Y, Wang Z, Qiang X, Zhao Q (2022) Synthesis, antiviral, and antibacterial activity of the glycyrrhizic acid and glycyrrhetinic acid derivatives. Russ J Bioorganic Chem 48:906–918. https://doi.org/10.1134/S1068162022050132

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Nagar PS, Rane S, Dwivedi M (2022) LC-MS/MS standardization and validation of glycyrrhizin from the roots of Taverniera cuneifolia: a potential alternative source of Glycyrrhiza glabra. Heliyon 8:e10234. https://doi.org/10.1016/j.heliyon.2022.e10234

Nascimento MHMD, de Araújo DR (2022) Exploring the pharmacological potential of glycyrrhizic acid: from therapeutic applications to trends in nanomedicine. Future Pharmacol 2:1–15. https://doi.org/10.3390/futurepharmacol2010001

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