The Influence of Monoammonium Salt of Glycyrrhizinic Acid and Acetylsalicylic Acid on Cardiac and Hematological Processes in Rats with Experimental Myocarditis
DOI:
https://doi.org/10.37134/jsml.vol13.1.14.2025Keywords:
Experimental myocarditis,, Monoammonium glycyrrhizinate (MASGA), , Acetylsalicylic acid (ASA), , Oxidative stress, , Myocardial injury,, Heart inflammationAbstract
This study investigated the effects of GLAS, a supramolecular complex composed of the monoammonium salt of glycyrrhizic acid and aspirin, on vascular-platelet hemostasis, lipid peroxidation (LPO), mitochondrial function, respiratory chain enzyme activity, and the NO-ergic system in an experimental model of adrenaline-induced myocarditis. In vitro, GLAS and aspirin at concentrations of 10⁻² and 10⁻³ mg/mL significantly reduced ADP-induced platelet aggregation by 2-3 times for aspirin and 2-5 times for GLAS. In vivo, GLAS transiently reduced platelet count and decreased adhesion by 42% and aggregation by 46%. Myocarditis led to a 98% increase in malondialdehyde (MDA), a key marker of LPO, while GLAS reduced MDA levels by 68% in myocardial cell homogenates and by 62.2% in cardiac mitochondria. Additionally, myocarditis impaired oxidative phosphorylation, reduced mitochondrial respiration, and inhibited succinate dehydrogenase and NAD dehydrogenase by 47.6% and 40.7%, respectively. GLAS and aspirin improved mitochondrial function, with GLAS showing greater efficacy in enhancing oxidative phosphorylation and stimulating enzyme activity. Moreover, myocarditis increased nitric oxide metabolite levels due to elevated inducible nitric oxide synthase (iNOS) activity, and GLAS more effectively reduced iNOS expression than aspirin, although it did not fully normalize the parameters. These findings suggest that GLAS, through its pronounced antioxidant and anti-inflammatory effects, offers protective benefits to cardiac muscle cells in myocarditis and may serve as a promising therapeutic agent for cardiovascular complications associated with this condition.
Downloads
References
Abo EMNF, El-Mesery M, El-Karef A, El-Shishtawy MM. (2018). Glycyrrhizin ameliorates high fat diet-induced
Akhmerov A, Marbán E. (2020). COVID-19 and the heart. Circulation Research, 126(10), 1443-1455.
Baltina LA. (2003). Chemical Modification of glyccyrrhizic ac id as route to new bioactive compounds for medicine. Journal of Current Medicinal Chemistry, 10, 231-237.
Baluda VP, Barkagan ZS, Gol'dberg ED. (1980). Laboratory Methods of Hemostasis System Research. Tomsk, Russia, p. 226-227.
Bonafede R. (2018). Manucha/Nitric oxide and related factors linked to oxidation and inflammation as possible biomarkers of heart failure. Clínica e Investigaciónen Arteriosclerosis, 30(2), 84-94.
Born GV. (1962). Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature, 194(4832), 927-929.
Brociek E, Tymińska A, Giordani AS, Caforio ALP, Wojnicz R, Grabowski M, Ozierański K. (2023). Myocarditis: Etiology, pathogenesis, and their implications in clinical practice. Biology, 12(6), 874.
Chance B, Williams, GR. (1955). A simple and rapid assay of oxidative phosphorylation. Nature, 175(4469), 1120-1121.
Costa AC, Reina-Couto M, Albino-Teixeira A, Sousa T. (2017). Aspirin and blood pressure: Effects when used alone or in combination with antihypertensive drugs. Revistaportuguesa de Cardiologia, 36, 551-567.
D’Oria R, Schipani R, Leonardini A, Natalicchio A, Perrini S, Cignarelli A. (2020). The role of oxidative stress in cardiac disease: From physiological response to injury factor. Oxidative Medicine and Cellular Longevity, 5732956.
Dalimova S, Kuziyev S, Umarova G, Mukhammadjonova G, Yunusova M, Khamdamova N. (2020). Influence of the supramolecular complex of glycyrrhizic acid with quercetin on age-related functional changes in rat brain mitochondria. Plant Cell Biotechnology and Molecular Biology, 45, 63-73.
Dolimova SN, Umarova GB, Mukhamadzhonova GM, Kuziyev SN, Yunusova M. (2018). Influence of supramolecular complexes, synthesized on the basis of natural compounds on the mitochondrial enzymes in rats of various ages. European Science Review, 3, 43-47.
Eichhorn C, Biere L, Schnell F, Schmied C, Wilhelm M, Kwong RY, Grani C. (2020). Myocarditis in athletes is a challenge. JACC Cardiovascular Imaging, 13(2), 494-507.
Ewid M. (2020). AST/ALT ratio predicts the functional severity of chronic heart failure with reduced left ventricular ejection fraction. BMC Research Notes, 13, 170-178
Falleti J, Orabona P, Municinò M, Castellaro G, Fusco G, Mansueto G. (2024). An update on myocarditis in forensic pathology. Diagnostics, 14(7), 760.
Feusner JH, BehrensJA, Detter JC, Cullen TC. (1979). Platelet counts in capillary blood. American Journal of Clinical Pathology, 72(3), 410-414.
Gostimskaya I, Galkin A. (2010). Preparation of highly coupled rat heart mitochondria. Journal of Visualized Experiments, 43, 2202.
Hennekens CH, Schneider WR, Pokov A, Hetzel S, Demets D, Serebruany V, Schröder H. (2010). A randomized trial of aspirin at clinically relevant doses and nitric oxide formation in humans. Journal of Cardiovascular Pharmacology and Therapeutics, 15(4), 344-348.
Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D, Dario S.C, Manuel C, Davide F, Emanuele GR, Marianna A, Enrico A, Gianfranco S, Carlo ML, Marco M. (2020). Cardiac involvement in a patient with Coronavirus disease 2019 (COVID-19). JAMA Cardiology, 5(7), 819-824.
Jannati S, Patnaik R, Banerjee Y. (2024). Beyond anticoagulation: A comprehensive review of non-vitamin K oral anticoagulants (NOACs) in inflammation and protease-activated receptor signaling. International Journal of Molecular Sciences, 25(16), 8727.
Khamdamova NA, Vipova NA, Kuziyev SN, Umarova GB, Yunusova MK, Mukhamadjonova GM, Khamroev SK, Urinov SD, Yalalova IR, Dalimova SN. (2024). Study of the antithrombotic effect of the ASA complex with the monoammonium salt of glycyrrhizic acid. Jornal of Theoretical and Clinical Medicine, 2, 47-52.
Kochi AN, Tagliari AP, Forleo GB, Fassini GM, Tondo C. (2020). Cardiac and arrhythmic complications in patients with COVID-19. Journal of Cardiovascular Electrophysiology, 31(5), 1003-1008.
Kuhl U, Schultheiss HP. (2009). Viral myocarditis: diagnosis, aetiology and management: Diagnosis, aetiology and management. Drugs, 69(10), 1287-1302.
Li JY, Cao HY, Liu P, Cheng GH, Sun MY. (2014). Glycyrrhizic acid in the treatment of liver diseases: literature review. Biomed Research International, 872139.
Li LQ, Huang T, Wang YQ, Wang ZP, Liang Y, Huang TB, Zhang H, Sun W, Wang Y. (2020). COVID-19 patients’ clinical characteristics, discharge rate, and fatality rate of meta-analysis. Journal of Medical Virology, 92(6), 577-583.
Li Y, Liu C, Fang B, Chen X, Wang K, Xin H, Wang K, Yang SM. (2024). Ferroptosis, a therapeutic target for cardiovascular diseases, neurodegenerative diseases and cancer. Journal of Translational Medicine, 22(1), 1137.
Lingappan K. (2018). NF-κB in Oxidative Stress. Current Opinion in Toxicology, 7, 81-86.
Long B, Brady WJ, Koyfman A, Gottlieb M. (2020). Cardiovascular complications in COVID-19. The American Journal of Emergency Medicine, 38(7), 1504-1507.
Lynge TH, Nielsen TS, Gregers Winkel B, Tfelt-Hansen J, Banner J. (2019). Sudden cardiac death caused by myocarditis in persons aged 1-49 years: a nationwide study of 14 294 deaths in Denmark. Forensic Sciences Research, 4(3), 247-256.
Maack C, Lehrke M, Backs J, Heinzel FR, Hulot JS, Marx N, Paulus WJ, Rossignol P, Taegtmeyer H, Bauersachs J, Bayes-Genis A, Brutsaert D, Bugger H, Clarke K, Cosentino F, De Keulenaer G, Dei Cas A, González A, Huelsmann M, Iaccarino G, Lunde IG, Lyon AR, Pollesello P, Rena G, Riksen NP, Rosano G, Staels B, van Laake LW, Wanner C, Farmakis D, Filippatos G, Ruschitzka F, Seferovic P, de Boer RA, Heymans S. (2018). Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology. European Heart Journal, 39(48), 4243-4254.
Mladenka P, Applova L, Patocka J, Costa VM, Remiao F, Pourova J, Mladenka A, Karlickova J, Jahodar L, Voprsalova M, Varner KJ, Sterba M. (2018). Comprehensive review of cardiovascular toxicity of drugs and related agents. Medicinal Research Reviews, 38(4), 1332-1403.
obesity in rats by activating NrF2 pathway. Life Sciences, 193, 159-170.
Pearce RM. (1906). Experimental myocarditis; A study of the histological changes following intravenous injections of adrenalin. The Journal of Experimental Medicine, 8(3), 400-409.
Peterson GL. (1977). A simplification of the protein assay method of Lowry. which is more generally applicable. Analytical Biochemistry, 83(2), 346-356.
Rashedinia M, Saberzadeh J, Khosravi BT, Hozhabri S, Arabsolghar R. (2019). Glycyrrhizic acid ameliorates mitochondrial function and biogenesis against aluminum toxicity in PC12 cells. Neurotoxicity Research, 35(3), 584-593.
Schror K, Rauch BH. (2015). Aspirin and lipid mediators in the cardiovascular system. Prostaglandins & Other Lipid Mediators, 121, 17-23.
Shi Q, Wang Q, Chen J, Xia F, Qiu C, Li M, Zhao M, Zhang Q, Luo P, Lu T, Zhang Y, Xu L, He X, Zhong T, Lin N, Guo Q, (2021). Transcriptome and lipid metabolomics-based discovery: Glycyrrhizic acid alleviates Tripterygium glycoside tablet-induced acute liver injury by regulating the activities of CYP and the metabolism of phosphoglycerides. Frontiers in Pharmacology, 12, 822154.
Tang Q, Cao Y, Xiong W, Ke X, Zhang J, Xia Y, Liu D. (2020). Glycyrrhizic acid exerts protective effects against hypoxia/reoxygenation-induced human coronary artery endothelial cell damage by regulating mitochondria. Experimental and Therapeutic Medicine, 20(1), 335-342.
Tolstikova TG, Khvostov MV, Bryzgalov AO. (2009). The complexes of drugs with carbohydrate-containing plant metabolites as pharmacologically promising agents. Mini Reviews in Medicinal Chemistry, 9(11), 1317-1328.
Totzeck M, Hendgen-Cotta UB, Rassaf T. (2017). Nitrite-nitric oxide signaling and cardioprotection. Advances in Experimental Medicine and Biology, 982, 335-346.
Treuer AV, Gonzalez DR. (2015). Nitric oxide synthases, S-nitrosylation and cardiovascular health: from molecular mechanisms to therapeutic opportunities. Molecular Medicine Reports, 11(3), 1555-1565.
Tschöpe C, Ammirati E, Bozkurt B, Caforio ALP, Cooper LT, Felix SB. (2021). Myocarditis and inflammatory cardiomyopathy: current evidence and future directions. Nature Reviews Cardiology, 18(3), 169-193.
Tymińska A, Ozierański K, Skwarek A, Kapłon-Cieślicka A, Baritussio A, Grabowski M. (2022). Personalized management of myocarditis and inflammatory cardiomyopathy in clinical practice. Journal of Personalized Medicine, 12(2), 183.
Wahab S, Annadurai S, Abullai SS, Das G, Ahmad W, Ahmad MF. (2021). Glycyrrhiza glabra (licorice): A comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicology. Plants, 10(12), 2751.
Yadav S, Singh A, Singhal R, Yadav JP. (2024). Revolutionizing drug discovery: The impact of artificial intelligence on advancements in pharmacology and the pharmaceutical industry. Intelligent Pharmacy, 2(3), 367-380.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Muslima Yunusova, Surayyo Dalimova, Sherali Kuziev, Gulbahor Umarova, Nigora Hamdamova, Guzal Mukhammadjonova, Mukhlisa Dadakhonova, Sobir Khamroev, Zaynieva Makhbuba, Gafurov Maxmudjon, Farkhod Eshboev
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
