Glycyrrhizic Acid Monoammonium Complex (XF-2): Chemical Profile and Immunomodulatory Evaluation

Authors

  • Fayyoza Khurramova A.S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan, Tashkent, Uzbekistan
  • Rakhmat Esanov National University of Uzbekistan, Tashkent, Uzbekistan
  • Izzatullo Abdullaev A.S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan, Tashkent, Uzbekistan
  • Ulugbek Gayibov A.S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan, Tashkent, Uzbekistan
  • Kuralbay Rezhepov A.S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan, Tashkent, Uzbekistan
  • Alimjan Matchanov A.S. Sadykov Institute of Bioorganic Chemistry of the Science Academy of Uzbekistan, Tashkent, Uzbekistan

DOI:

https://doi.org/10.48048/tis.2026.12285

Keywords:

Glycyrrhizic acid monoammonium salt, Supramolecular complex, UV-Vis and FTIR spectroscopy, Molecular docking, NF-κB p52, Immunomodulatory activity, Low toxicity, Prednisolone-induced immunosuppression, Glycyrrhizic acid monoammonium salt, Supramolecular complex, UV-Vis and FTIR spectroscopy, Molecular docking, NF-κB p52, Immunomodulatory activity, Low toxicity, Prednisolone-induced immunosuppression

Abstract

This study explores the physicochemical and biological properties of the supramolecular complex XF-2, composed of glycyrrhizic acid monoammonium salt and anti-tuberculosis drugs pyrazinamide, isoniazid, rifampicin, and levofloxacin. UV-Vis spectroscopy revealed a bathochromic shift from 254 to 264 nm, confirming electronic interactions between glycyrrhizic acid and the guest molecules. FTIR spectra showed characteristic bands at 1,658 cm⁻¹ (C=O) and 1,593 cm⁻¹ (–COO⁻), indicating ionic and hydrogen-bonded interactions responsible for supramolecular assembly formation. Molecular docking analysis demonstrated stable binding of XF-2 components with NF-κB p52 (2AZ5), IL-10 (1VLK), and IL-6 receptor (1A3Q), with binding energies ranging from –4.6 to –9.2 kcal/mol. Rifampicin and levofloxacin exhibited the strongest affinities, forming multiple hydrogen bonds, π-π stacking, and electrostatic interactions with key amino acid residues. In vivo studies showed that XF-2 is low-toxic (LD₅₀ = 4,050 mg/kg) and exerts marked immunomodulatory activity in prednisolone-induced immunosuppressed mice. At 1,000 mg/kg, the complex significantly increased thymus and spleen indices, restoring immune organ weights close to normal values. Together, spectroscopic, computational, and pharmacological data confirm that XF-2 is a stable, safe, and biologically active supramolecular formulation with strong immunorestorative potential, making it a promising candidate for further development as an immunomodulatory and protective agent.

HIGHLIGHTS

  • The supramolecular complex XF-2 was formed with glycyrrhizic acid monoammonium salt.
  • UV-Vis and FTIR spectra confirmed hydrogen-bonded and ionic complex formation.
  • Docking showed strong binding to NF-κB p52, IL-10, and IL-6 receptor proteins.
  • XF-2 exhibited low acute toxicity (LD₅₀ = 4050 mg/kg) in in vivo preclinical tests.
  • The complex restored thymus and spleen indices, showing potent immunomodulatory activity.

GRAPHICAL ABSTRACT

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References

RS Esanov, AZ Dzhuraev, KS Rafikova, Z Khashimova, E Berdibaev, D Abdurazzakova and A Matchanov. Synthesis and biological activity of some esters of glycyrretinic acid. Engineered Science 2024; 31, 1212.

KA Yuldashev, RS Esanov, HT Saidullaeva, VV Uzbekov, MK Salakhutdinova, ZS Khashimova, MB Gafurov, YI Oshchepkova and SI Salikhov. Creation of modified forms of amiodarone with glycyrrhizic acid and its monoammonium salt and study of their cytotoxicity on HeLa cells. Pharmaceutical Chemistry Journal 2024; 57, 1726-1731.

MB Rakhimova, RS Esanov, PG Merzlyak, MB Gafurov, RS Kurbannazarova, OD Matchanov and RZ Sabirov. Effect of glycyrrhetic acid derivatives on regulation of thymocyte volume. Bulletin of Experimental Biology and Medicine, 2023; 175(1), 27-31.

RS Esanov, KM Bobakulov, ND Abdullaev, MB Gafurov and KA Yuldashev. Synthesis of new 18β-H-glycyrrhetic acid amides with several 2-amino-5-alkylaminothiadiazoles. Chemistry of Natural Compounds 2021; 57, 335-338.

DT Babaeva, RS Esanov, AA Akhunov, MB Gafurov, NR Khashimova and AD Matchanov. Biological activity of the supramolecular complex of glycyrrhizic and salicylic acids. Chemistry of Natural Compounds, 2020; 56(2), 278-281.

AD Matchanov, DN Dalimov, UN Zainutdinov, NL Vypova, AK Islamov and BM Bekpolatova. Preparation and physicochemical and biological properties of molecular associates of lagochilin and lagochirsine with glycyrrhizic acid and its monoammonium salt. Chemistry of Natural Compounds 2020; 53(4), 665-669.

AD Matchanov, RS Esanov, T Renkawitz, AB Soliev, E Kunisch, I Gonzalo de Juan, F Westhauser and DU Tulyaganov. Synthesis, structure-property evaluation and biological assessment of supramolecular assemblies of bioactive glass with glycyrrhizic acid and its monoammonium salt. Materials 2022; 15(12), 4197.

Mamajanov, M., Abdullaev, I., Sotimov, G., Mavlanova, S., Niyozov, Q., Mirzaolimov, M., Najimov, A., Mirzaolimov, E., Raximberganov, M, & Abdullayev, U. Mitochondrial and Pharmacokinetic Insights into 3,5,7,2’,6’-Pentahydroxyflavanone: Respiratory Modulation, Calcium Handling, and Membrane Stability. Trends in Sciences, 2025; 22(12), 10984.

Aripov, T.F., Gayibov, U.G., Gaibova, S.N. et al. In Vitro Antioxidant and Antiradical Activity of Rutan, a Polyphenolic Extract from the Tannic Sumach (Rhus coriaria L.) Leaves. Russ J Bioorg Chem, 2025; 51, 3077–3085

Li, M., Zhang, M., Fatixovich, A.T. et al. Green-synthesized Zn²⁺-polyphenol networks (CGA/RA) for enhanced multifunctional food preservation. Food Measure (2025).

Ulugbek G, Izzatullo A, Fotima S, Sirojiddin O, Azizbek A, Sabina G, et al. Plant derived and synthetical antihypoxic agents in cardiovascular diseases: Mechanisms, key pathways and therapeutic potential. Plant Sci. Today. 2025; 12(4).

I Abdullaev, U Gayibov, S Omonturdiev, S Fotima, S Gayibova and T Aripov. Molecular pathways in cardiovascular disease under hypoxia: Mechanisms, biomarkers, and therapeutic targets. The Journal of Biomedical Research 2025; 39(3), 254-269.

AA Abdullaev, DR Inamjanov, DS Abduazimova, SZ Omonturdiyev, UG Gayibov, SN Gayibova and TF Aripov. Sílybum mariánum’s impact on physiological alterations and oxidative stress in diabetic rats. Biomedical and Pharmacology Journal 2024; 17(2), 1291-1300.

AV Mahmudov, OS Abduraimov, SB Erdonov, UG Gayibov and LY Izotova. Bioecological features of Nigella sativa L. in different conditions of Uzbekistan. Plant Science Today 2022; 9(2), 421-426.

AZ Dzhuraev, RS Esanov, AA Ganiev, KM Bobakulov, ND Abdullaev and AD Matchanov. Synthesis of new amides of 3-O-acetyl-18β-H-glycyrrhetic acid. Chemistry of Natural Compounds 2024; 60(1), 80-83.

AQQ Azimova, AX Islomov, SA Maulyanov, DG Abdugafurova, LU Mahmudov, IZ Abdullaev, AS Ishmuratova, SQQ Siddikova and IR Askarov. Determination of vitamins and pharmacological properties of Vitis vinifera L. syrup-honey. Biomedical and Pharmacology Journal 2024; 17(4), 2779-2786.

AD Matchanov, FN Tashpulatov, FA Sobirova, AV Filatova, RS Esanov, KV Raimova and NL Vypova. Hemostatic activity of “Glilagel” gel based on lagochilin with monoammonium salt of glycyrrhizic acid. Experimental and Clinical Pharmacology 2020; 83(11), S20-S22.

E Pashkina, V Evseenko, N Dumchenko, M Zelikman, A Aktanova, M Bykova, M Khvostov, A Dushkin and V Kozlov. Preparation and characterization of a glycyrrhizic acid-based drug delivery system for allergen-specific immunotherapy. Nanomaterials 2021; 12(1), 148.

YG Sıdır and I Sıdır. Optical properties, UV-Vis absorption and fluorescence spectra of 4-pentylphenyl 4-n-benzoate derivatives in different solvents. Journal of Fluorescence 2025; 12(1), 148.

O Gaibullayeva, A Islomov, D Abdugafurova, B Elmurodov, B Mirsalixov, L Mahmudov, I Abdullaev, K Baratov, S Omonturdiev and S Sa’dullayeva. Inula helenium L. root extract in sunflower oil: Determination of water-soluble vitamins and immunity-promoting effect. Biomedical and Pharmacology Journal 2024; 17(4), 2729-2737.

A Abdullaev, I Abdullaev, A Bogbekov, U Gayibov, S Omonturdiev, S Gayibova, M Turahodjayev, K Ruziboev and T Aripov. Antioxidant potential of Rhodiola heterodonta extract: Activation of Nrf2 pathway via integrative in vivo and in silico studies. Trends in Sciences 2025; 22(5), 9521.

OS Zoirovich, AIZ Ugli, ID Raxmatillayevich, ML Umarjonovich, ZM Ravshanovna and G Sabina. The effect of Ajuga turkestanica on the rat aortic smooth muscle ion channels. Biomedical and Pharmacology Journal 2024; 17(2), 1213-1222.

D Inomjonov, I Abdullaev, S Omonturdiev, A Abdullaev, L Maxmudov, M Zaripova, M Abdullayeva, D Abduazimova, S Menglieva, S Gayibova, M Sadbarxon, U Gayibov and T Aripov. In vitro and in vivo studies of Crataegus and Inula helenium extracts: Their effects on rat blood pressure. Trends in Sciences 2025; 22(3), 9158.

S Sodiqova, S Kadirova, A Zaynabiddinov, I Abdullaev, L Makhmudov, U Gayibov, M Yuldasheva, M Xolmirzayeva, R Rakhimov, A Mutalibov and H Karimjonov. Channelopathy activity of A-41 (propyl ester of gallic acid): Experimental and computational study of antihypertensive activity. Trends in Sciences 2025; 22(9), 10496.

R Sayidaliyeva, S Kadirova, A Zaynabiddinov, I Abdullaev, L Makhmudov, U Gayibov, M Yuldasheva, M Kholmirzayeva, R Rakhimov, A Mutalibov and H Karimjonov. A-51 as a natural calcium channel blocker: An integrative study targeting hypertension. Trends in Sciences 2025; 22(11), 10760.

A Khasanov, I Abdullaev, S Kadirova, M Mamajanov, A Zaynabiddinov, S Omonturdiev, L Makhmudov, D Inomjonov, U Gayibov, R Esanov and A Matchanov. N-2 polyphenol targets vascular calcium channels to exert antihypertensive effects: In vitro and in vivo evaluation. Trends in Sciences 2025; 22(12), 10782.

O Trott and AJ Olson. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry 2010; 31(2), 455-461.

M Zaripova, I Abdullaev, A Bogbekov, U Gayibov, S Omonturdiev, R Makhmudov, N Ergashev, G Jabbarova, S Gayibova and T Aripov. In vitro and in silico studies of Gnaphalium uliginosum extract: Inhibition of α-amylase and α-glucosidase as a potential strategy for metabolic syndrome regulation. Trends in Sciences 2025; 22(8), 10098.

UG Gayibov, SN Gayibova, DS Abduazimova, RN Rakhimov, HS Ruziboev, MA Xolmirzayeva, AE Zaynabiddinov and TF Aripov. Antioxidant and cardioprotective properties of polyphenolic plant extract of Rhus glabra L. Plant Science Today 2024; 11(3), 2348-1900.

TF Aripov and UG Gayibov. Antiradical and antioxidant activity of the preparation “Rutan” from Rhus coriaria L. Journal of Theoretical and Clinical Medicine 2023; 4, 164-170.

MR Zaripova, SN Gayibova, RR Makhmudov, AA Mamadrahimov, NL Vypova, UG Gayibov, SM Miralimova and TF Aripov. Characterization of Rhodiola heterodonta (Crassulaceae): Phytocomposition, antioxidant and antihyperglycemic activities. Preventive Nutrition and Food Science 2024; 29(2), 135-145.

AV Mahmudov, OS Abduraimov, SB Erdonov, AL Allamurotov, OT Mamatkasimov, UG Gayibov and LY Izotova. Seed productivity of Linum usitatissimum L. in different ecological conditions of Uzbekistan. Plant Science Today 2022; 9(4), 1090-1101.

A Sandoo, JJCSV van Zanten, GS Metsios, D Carroll and GD Kitas. The endothelium and its role in regulating vascular tone. The Open Cardiovascular Medicine Journal 2010; 4, 302-312.

TF Aripov, UG Gayibov, SN Gaibova, YI Oshchepkova and SI Salikhov. In vitro antioxidant and antiradical activity of the total polyphenols of Rhus coriaria L. leaves (substances of the antiviral drug “Rutan”). Khimiya Rastitel’nogo Syr’ya 2024; 4, 138-148.

UG Gayibov, EJ Komilov, RN Rakhimov, NA Ergashev, NG Abdullajanova, MI Asrorov and TF Aripov. Influence of a new polyphenol compound from Euphorbia plant on mitochondrial function. Journal of Microbiology, Biotechnology and Food Sciences 2019; 8(4), 1021-1025.

Y Umidakhon, B Erkin, G Ulugbek, N Bahadir and A Karim. Correction of mitochondrial NADH oxidase activity, peroxidation and phospholipid metabolism by haplogenin-7-glucoside in hypoxia and ischemia. Trends in Sciences 2022; 19(21), 6260.

MK Pozilov, U Gayibov, MI Asrarov, NG Abdulladjanova, HS Ruziboev and TF Aripov. Physiological alterations of mitochondria under diabetes condition and its correction by polyphenol gossitan. Journal of Microbiology, Biotechnology and Food Sciences 2022; 12(2), 2224.

AG Vakhobjonovna, KE Jurayevich, AIZ Ogli, EN Azamovich, MR Rasuljonovich and AM Islomovich. Tannins as modulators in the prevention of mitochondrial dysfunction. Trends in Sciences 2025; 22(8), 10436.

Z Shakiryanova, R Khegay, U Gayibov, A Saparbekova, Z Konarbayeva, A Latif and O Smirnova. Isolation and study of a bioactive extract enriched with anthocyanin from red grape pomace (Cabernet Sauvignon). Agronomy Research 2023; 21(3), 1293-1303.

U Gayibov, SN Gayibova, KP Ma'murjon, FS Tuxtaeva, UR Yusupova, GMK Djabbarova, ZA Mamatova, NA Ergashev and TF Aripov. Influence of quercetin and dihydroquercetin on some functional parameters of rat liver mitochondria. Journal of Microbiology, Biotechnology and Food Sciences 2021; 11(1), e2924.

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Published

2026-01-20

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