Impact of licorice supplementation on cardiac biomarkers and histomorphological changes in rats
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Liu Yuzhu
, Rosfayati Othman
Abstract
Objectives
This study aimed to evaluate the impact of oral licorice supplementation on cardiotoxic biomarkers and histological changes in cardiac tissue in rats, given the widespread use of licorice (Glycyrrhiza glabra) for its anti-inflammatory, antioxidant, and antimicrobial properties and the concerns about its cardiotoxic effects at higher doses or with short-term repeated use.
Methods
Twenty-four female Sprague-Dawley rats were divided into four groups (n=6 per group). Groups received either distilled water or licorice extract at 50, 100, and 200 mg/kg/day for 14 days. Cardiac tissue was analyzed via H&E staining, and blood samples were assessed for Troponin-T and Pro-BNP levels.
Results
No significant changes were observed in Troponin-T and Pro-BNP levels across all groups (p>0.05). Histological analysis revealed mild changes in the cardiac tissues of rats treated with licorice, indicating subtle histomorphological alterations.
Conclusions
Licorice supplementation at doses of 50, 100, and 200 mg/kg/day did not significantly impact the levels of cardiotoxic biomarkers but mild histomorphological changes were observed in the cardiac tissues of rats. These findings suggest that while licorice is generally safe at these doses, its long-term use at high doses should be approached with caution.
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Research ethics: The experimental procedures of the animal studies were approved by the University of Tunku Abdul Rahman (Ethics Number U/SERC/253/2022).
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Informed consent: Not applicable.
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Author contributions: All authors contributed to the study, accepted responsibility for the entire content of this manuscript, and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors declare no conflict of interest.
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Research funding: The research work was financially supported by the MAHSA University for their support, made possible through the MAHSA Research Grant (RP194-10/22).
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Data availability: Not applicable.
References
1. Abo-Samaha, MI, Alghamdi, YS, El-Shobokshy, SA, Albogami, S, ElMaksoud, EMA, Farrag, F, et al.. Licorice extract supplementation affects antioxidant activity, growth-related genes, lipid metabolism, and immune markers in broiler chickens. Life (Basel) 2022;12:914. https://doi.org/10.3390/life12060914.Suche in Google Scholar PubMed PubMed Central
2. Ahmed-Farid, OA, Haredy, SA, Niazy, RM, Linhardt, RJ, Warda, M. Dose-dependent neuroprotective effect of oriental phyto-derived glycyrrhizin on experimental neuroterminal norepinephrine depletion in a rat brain model. Chem Biol Interact 2019;308:279–87. https://doi.org/10.1016/j.cbi.2019.05.045.Suche in Google Scholar PubMed
3. Assar, DH, Elhabashi, N, Mokhbatly, AA, Ragab, AE, Elbialy, ZI, Rizk, SA, et al.. Wound healing potential of licorice extract in rat model: antioxidants, histopathological, immunohistochemical, and gene expression evidences. Biomed Pharmacother 2021;143:112151. https://doi.org/10.1016/j.biopha.2021.112151.Suche in Google Scholar PubMed
4. Berry, JD, Nambi, V, Ambrosius, WT, Chen, H, Killeen, AA, Taylor, A, et al.. Associations of high-sensitivity troponin and natriuretic peptide levels with outcomes after intensive blood pressure lowering: findings from the SPRINT randomized clinical trial. JAMA Cardiol 2021;6:1397–405. https://doi.org/10.1001/jamacardio.2021.3187.Suche in Google Scholar PubMed PubMed Central
5. Chen, G, Luo, S, Guo, H, Lin, J, Xu, S. Licochalcone A alleviates ferroptosis in doxorubicin-induced cardiotoxicity via the PI3K/AKT/MDM2/p53 pathway. Naunyn-Schmiedebergs Arch Pharmacol 2024;397:4247–62. https://doi.org/10.1007/s00210-023-02863-1.Suche in Google Scholar PubMed
6. Cheng, Y, Chen, Z, Yang, S, Liu, T, Yin, L, Pu, Y, et al.. Nanomaterials-induced toxicity on cardiac myocytes and tissues, and emerging toxicity assessment techniques. Sci Total Environ 2021;800:149584. https://doi.org/10.1016/j.scitotenv.2021.149584.Suche in Google Scholar PubMed
7. Cheng, Y, Wu, X, Nie, X, Wu, Y, Zhang, C, Lee, SMY, et al.. Natural compound glycyrrhetinic acid protects against doxorubicin-induced cardiotoxicity by activating the Nrf2/HO-1 signaling pathway. Phytomedicine 2022;106:154407. https://doi.org/10.1016/j.phymed.2022.154407.Suche in Google Scholar PubMed
8. Choi, HJ, Seon, MR, Lim, SS, Kim, JS, Chun, HS, Park, JH. Hexane/ethanol extract of Glycyrrhiza uralensis licorice suppresses doxorubicin-induced apoptosis in H9c2 rat cardiac myoblasts. Exp Biol Med (Maywood) 2008;233:1554–60. https://doi.org/10.3181/0807-rm-221.Suche in Google Scholar
9. Deutch, MR, Grimm, D, Wehland, M, Infanger, M, Krüger, M. Bioactive candy: effects of licorice on the cardiovascular system. Foods 2019;8:495. https://doi.org/10.3390/foods8100495.Suche in Google Scholar PubMed PubMed Central
10. Garg, M, Singhal, T, Sharma, H. Cardioprotective effect of ammonium glycyrrhizinate against doxorubicin-induced cardiomyopathy in experimental animals. Indian J Pharmacol 2014;46:527–30. https://doi.org/10.4103/0253-7613.140585.Suche in Google Scholar PubMed PubMed Central
11. Zhang, X, Qiu, H, Li, C, Cai, P, Qi, F. The positive role of traditional Chinese medicine as an adjunctive therapy for cancer. Biosci Trends 2021;15:283–98. https://doi.org/10.5582/bst.2021.01318.Suche in Google Scholar PubMed
12. Cui, Q, Wang, W, Shi, J, Lai, F, Luo, S, Du, Y, et al.. Glycyrrhizin ameliorates cardiac injury in rats with severe acute pancreatitis by inhibiting ferroptosis via the Keap1/Nrf2/HO-1 pathway. Dig Dis Sci 2024;69:2477–87. https://doi.org/10.1007/s10620-024-08398-6.Suche in Google Scholar PubMed
13. Gu, X, Shi, Y, Chen, X, Sun, Z, Luo, W, Hu, X, et al.. Isoliquiritigenin attenuates diabetic cardiomyopathy via inhibition of hyperglycemia-induced inflammatory response and oxidative stress. Phytomedicine 2020;78:153319. https://doi.org/10.1016/j.phymed.2020.153319.Suche in Google Scholar PubMed
14. Haney, D, Ma, Y, Dalmacy, D, Pajewski, NM, Hajjar, I, de Lemos, JA, et al.. High-sensitivity troponin T, NT-proBNP, and cognitive outcomes in SPRINT. Hypertension 2024;81:1956–65. https://doi.org/10.1161/hypertensionaha.124.22876.Suche in Google Scholar
15. Hossain, F, Mostofa, MG, Alam, AK. Traditional uses and pharmacological activities of the genus leea and its phytochemicals: a review. Heliyon 2021;7:e06222. https://doi.org/10.1016/j.heliyon.2021.e06222.Suche in Google Scholar PubMed PubMed Central
16. Hosseini, A, Sahebkar, A. Reversal of doxorubicin-induced cardiotoxicity by using phytotherapy: a review. J Pharmacopuncture 2017;20:243–56. https://doi.org/10.3831/KPI.2017.20.030.Suche in Google Scholar PubMed PubMed Central
17. Hosseini, A, Shafiee-Nick, R, Mousavi, SH. Combination of Nigella sativa with Glycyrrhiza glabra and Zingiber officinale augments their protective effects on doxorubicin-induced toxicity in h9c2 cells. Iran J Basic Med Sci 2014;17:993–1000.Suche in Google Scholar
18. Izumi-Nakaseko, H, Chiba, K, Goto, A, Kambayashi, R, Matsumoto, A, Takei, Y, et al.. Electropharmacological characterization of licorice using the human induced pluripotent stem cell-derived cardiomyocytes sheets and the chronic atrioventricular block dogs. Cardiovasc Toxicol 2023;23:207–17. https://doi.org/10.1007/s12012-023-09795-5.Suche in Google Scholar PubMed
19. Jafari, F, Jafari, M, Moghadam, AT, Emami, SA, Jamialahmadi, T, Mohammadpour, AH, et al.. A review of Glycyrrhiza glabra (licorice) effects on metabolic syndrome. Adv Exp Med Biol 2021;1328:385–400. https://doi.org/10.1007/978-3-030-73234-9_25.Suche in Google Scholar PubMed
20. Wang, J, Chen, G. Dimethylacetamide-induced toxic hepatitis in spandex workers: clinical presentation and treatment outcomes. QJM 2020;113:324–9. https://doi.org/10.1093/qjmed/hcz282.Suche in Google Scholar PubMed
21. Kiani, Z, Amini, S, Askari, G, Kesharwani, P, Bagherniya, M, Sahebkar, A. The effect of phytochemicals in prediabetic patients: a systematic review of randomized controlled trials. Phytother Res 2023;37:3239–61. https://doi.org/10.1002/ptr.7892.Suche in Google Scholar PubMed
22. Lai, T, Shen, Y, Chen, C, Huang, B, Deng, T, Zhao, Z, et al.. Glycyrrhizic acid ameliorates myocardial ischemia-reperfusion injury in rats through inhibiting endoplasmic reticulum stress. Eur J Pharmacol 2021;908:174353. https://doi.org/10.1016/j.ejphar.2021.174353.Suche in Google Scholar PubMed
23. Li, M, Wen, Z, Xue, Y, Han, X, Ma, D, Ma, Z, et al.. Cardioprotective effects of glycyrrhizic acid involve inhibition of calcium influx via L-type calcium channels and myocardial contraction in rats. Naunyn-Schmiedebergs Arch Pharmacol 2020;393:979–89. https://doi.org/10.1007/s00210-019-01767-3.Suche in Google Scholar PubMed
24. Simmler, C, Pauli, GF, Chen, SN. Phytochemistry and biological properties of glabridin. Fitoterapia 2013;90:160–84. https://doi.org/10.1016/j.fitote.2013.07.003.Suche in Google Scholar PubMed PubMed Central
25. Jiang, M, Zhao, S, Yang, S, Lin, X, He, X, Wei, X, et al.. An essential herbal medicine-licorice: a review of phytochemicals and its effects in combination preparations. J Ethnopharmacol 2021;279:114362. Erratum in: J Ethnopharmacol. 2022;299:115706.10.1016/j.jep.2022.115706Suche in Google Scholar PubMed
26. Lin, PH, Chiang, YF, Shieh, TM, Chen, HY, Shih, CK, Wang, TH, et al.. Dietary compound isoliquiritigenin, an antioxidant from licorice, suppresses triple-negative breast tumor growth via apoptotic death program activation in cell and xenograft animal models. Antioxidants (Basel) 2020;9:228. https://doi.org/10.3390/antiox9030228.Suche in Google Scholar PubMed PubMed Central
27. Liu, C, Ma, X, Zhuang, J, Liu, L, Sun, C. Cardiotoxicity of doxorubicin-based cancer treatment: what is the protective cognition that phytochemicals provide us? Pharmacol Res 2020;160:105062. https://doi.org/10.1016/j.phrs.2020.105062.Suche in Google Scholar PubMed
28. Liu, Y, Wu, H, Zhou, G, Zhang, D, Yang, Q, Li, Y, et al.. Role of M6a methylation in myocardial ischemia-reperfusion injury and doxorubicin-induced cardiotoxicity. Cardiovasc Toxicol 2024;24:918–28. https://doi.org/10.1007/s12012-024-09898-7.Suche in Google Scholar PubMed
29. Mou, SQ, Zhou, ZY, Feng, H, Zhang, N, Lin, Z, Aiyasiding, X, et al.. Liquiritin attenuates lipopolysaccharides-induced cardiomyocyte injury via an AMP-activated protein kinase-dependent signaling pathway. Front Pharmacol 2021;12:648688. https://doi.org/10.3389/fphar.2021.648688.Suche in Google Scholar PubMed PubMed Central
30. Ojha, SK, Sharma, C, Golechha, M, Bhatia, J, Kumari, S, Arya, DS. Licorice treatment prevents oxidative stress, restores cardiac function, and salvages myocardium in rat model of myocardial injury. Toxicol Ind Health 2015;31:140–52. https://doi.org/10.1177/0748233713491800.Suche in Google Scholar PubMed
31. Aakre, KM, Omland, T. Physical activity, exercise and cardiac troponins: clinical implications. Prog Cardiovasc Dis 2019;62:108–15. https://doi.org/10.1016/j.pcad.2019.02.005.Suche in Google Scholar PubMed
32. Sun, P, Chen, H, Fan, X, Wang, J, Lu, L, Yang, G, et al.. Exploring the effective components of honey-processed licorice (Glycyrrhiza uralensis fisch.) in attenuating doxorubicin-induced myocardial cytotoxicity by combining network pharmacology and in vitro experiments. J Ethnopharmacol 2024;329:118178. https://doi.org/10.1016/j.jep.2024.118178.Suche in Google Scholar PubMed
33. Tang, Q, Cao, Y, Xiong, W, Ke, X, Zhang, J, Xia, Y, et al.. Glycyrrhizic acid exerts protective effects against hypoxia/reoxygenation-induced human coronary artery endothelial cell damage by regulating mitochondria. Exp Ther Med 2020;20:335–42. https://doi.org/10.3892/etm.2020.8668.Suche in Google Scholar PubMed PubMed Central
34. Thakur, V, Alcoreza, N, Delgado, M, Joddar, B, Chattopadhyay, M. Cardioprotective effect of glycyrrhizin on myocardial remodeling in diabetic rats. Biomolecules 2021;11:569. https://doi.org/10.3390/biom11040569.Suche in Google Scholar PubMed PubMed Central
35. Turan, C, Dogan, E, Yurtseven, A, Saz, EU. Usefulness of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) as a marker for cardiotoxicity and comparison with echocardiography in paediatric carbon monoxide poisoning. Cardiol Young 2020;30:1103–8. https://doi.org/10.1017/s1047951120001651.Suche in Google Scholar
36. Upadhyay, S, Mantha, AK, Dhiman, M. Glycyrrhiza glabra (licorice) root extract attenuates doxorubicin-induced cardiotoxicity via alleviating oxidative stress and stabilising the cardiac health in H9c2 cardiomyocytes. J Ethnopharmacol 2020;258:112690. https://doi.org/10.1016/j.jep.2020.112690.Suche in Google Scholar PubMed
37. He, M, Qu, L, Li, C, Chen, C, Huang, Y. Glycyrrhizic acid reduces doxorubicin-induced cardiotoxicity by modulating gut microbiota and NLRP3 inflammasome. Front Pharmacol 2022;13:999327.Suche in Google Scholar
38. Hu, B, Zhen, D, Bai, M, Xuan, T, Wang, Y, Liu, M, et al.. Ethanol extracts of Rhaponticum uniflorum (L.) DC flowers attenuate doxorubicin-induced cardiotoxicity via alleviating apoptosis and regulating mitochondrial dynamics in H9c2 cells. J Ethnopharmacol 2022;288:114936. https://doi.org/10.1016/j.jep.2021.114936.Suche in Google Scholar PubMed
39. Wang, KL, Yu, YC, Chen, HY, Chiang, YF, Ali, M, Shieh, TM, et al.. Recent advances in Glycyrrhiza glabra (Licorice)-containing herbs alleviating radiotherapy- and chemotherapy-induced adverse reactions in cancer treatment. Metabolites 2022;12:535. https://doi.org/10.3390/metabo12060535.Suche in Google Scholar PubMed PubMed Central
40. Wang, Z, Chen, Y, Gu, M, Wu, Z, Ding, B, Yang, W, et al.. Protective effects and mechanisms of lycorine against adriamycin-induced cardiotoxicity. Phytomedicine 2022;102:154178. https://doi.org/10.1016/j.phymed.2022.154178.Suche in Google Scholar PubMed
41. Wang, W, Yu, Y, Chen, H, Sun, P, Lu, L, Yan, S, et al.. Anti-arrhythmia potential of honey-processed licorice in zebrafish model: Antioxidant, histopathological and tissue distribution. J Ethnopharmacol 2023;316:116724. https://doi.org/10.1016/j.jep.2023.116724.Suche in Google Scholar PubMed
42. Watts, SW, Darios, ES, Contreras, GA, Garver, H, Fink, GD. Male and female high-fat diet-fed dahl SS rats are largely protected from vascular dysfunctions: PVAT contributions reveal sex differences. Am J Physiol Heart Circ Physiol 2021;321:H15–28. https://doi.org/10.1152/ajpheart.00131.2021.Suche in Google Scholar PubMed PubMed Central
43. Reda, FM, El-Saadony, MT, El-Rayes, TK, Farahat, M, Attia, G, Alagawany, M. Dietary effect of licorice (Glycyrrhiza glabra) on quail performance, carcass, blood metabolites and intestinal microbiota. Poult Sci 2021;100:101266. https://doi.org/10.1016/j.psj.2021.101266.Suche in Google Scholar PubMed PubMed Central
44. Saldarreaga Marin, A, Cendros, M, Ciudad, CJ, Sabater, A. Case report: Fatigue and bleeding in a polymedicated patient using several herbal supplementations, detected with g-Nomic® software. Pharmgenomics Pers Med 2021;14:963–70. https://doi.org/10.2147/pgpm.s323463.Suche in Google Scholar
45. Rodríguez Castillo, B, Cendrós, M, Ciudad, CJ, Sabater, A. Comprehensive analysis of drug utilization patterns, gender disparities, lifestyle influences, and genetic factors: insights from elderly cohort using g-Nomic® software. Pharmaceuticals (Basel) 2024;17:565. https://doi.org/10.3390/ph17050565.Suche in Google Scholar PubMed PubMed Central
46. Alagawany, M, El-Saadony, MT, Elnesr, SS, Farahat, M, Attia, G, Madkour, M, et al.. Use of lemongrass essential oil as a feed additive in quail’s nutrition: its effect on growth, carcass, blood biochemistry, antioxidant and immunological indices, digestive enzymes and intestinal microbiota. Poult Sci 2021;100:101172. https://doi.org/10.1016/j.psj.2021.101172.Suche in Google Scholar PubMed PubMed Central
47. Abo Ghanima, MM, Swelum, AA, Shukry, M, Ibrahim, SA, Abd El-Hack, ME, Khafaga, AF, et al.. Impacts of tea tree or lemongrass essential oils supplementation on growth, immunity, carcass traits, and blood biochemical parameters of broilers reared under different stocking densities. Poult Sci 2021;100:101443. https://doi.org/10.1016/j.psj.2021.101443.Suche in Google Scholar PubMed PubMed Central
48. Obeidat, MD, Alkhateeb, MEM, Jawasreh, KI, Riley, DG, Al Sukhni, IA. Herbal extract dietary supplementation effect on growth performance and meat quality in broiler raised under two stocking densities. Sci Rep 2024;14:18633. https://doi.org/10.1038/s41598-024-68138-8.Suche in Google Scholar PubMed PubMed Central
49. Elbaz, AM, El-Sonousy, NK, Arafa, AS, Sallam, MG, Ateya, A, Abdelhdy, AY. Oregano essential oil and Bacillus subtilis role in enhancing broiler’s growth, stress indicators, intestinal integrity, and gene expression under high stocking density. Sci Rep 2024;14:25411. https://doi.org/10.1038/s41598-024-75533-8.Suche in Google Scholar PubMed PubMed Central
50. Reda, FM, Alagawany, M, Mahmoud, HK, Mahgoub, SA, Elnesr, SS. Use of red pepper oil in quail diets and its effect on performance, carcass measurements, intestinal microbiota, antioxidant indices, immunity and blood constituents. Animal 2020;14:1025–33. https://doi.org/10.1017/s1751731119002891.Suche in Google Scholar
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