Investigating the cardioprotective effects of Illicium verum Against doxorubicin-induced cardiotoxicity in rats

Document Type : Research Paper

Author

Department of Biology, College of Education for Pure Sciences, University of Anbar, Ramadi, Anbar 31001, Iraq.

10.22103/jab.2026.26830.1851

Abstract

Objective
One of the chemotherapy drugs used to treat many cancers in the world is doxorubicin (DOX). However, this drug cannot be used indefinitely for treatment. Because it can cause dose-dependent cardiotoxicity. This toxicity causes inflammation and damage to cardiac tissue and oxidative stress. Therefore, the aim of our study was to investigate the potential cardioprotective effects of Illicium verum extract against DOX-induced cardiotoxicity in rats.
Materials and methods
Four groups of mice that were randomly selected were used in this experiment. These four groups included the control group, the DOX-treated group, the 100 mg/kg Illicium verum extract treatment group, and the 200 mg/kg Illicium verum extract treatment group. The extract was administered orally for 7 days. Then, DOX injection was performed. The extract was administered orally for 7 days after the injection. Serum cardiac biomarkers including cardiac troponin-I (cTn-I), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH) were measured to assess cardiac injury. To complete the evaluations, we also measured inflammatory cytokines (IL-6 and TNF-α), oxidative stress markers (malondialdehyde (MDA) and myeloperoxidase (MPO)), and antioxidant parameters (glutathione (GSH) and nitric oxide (NO)). To assess structural damage to cardiac tissue, we also performed histopathological studies.
Results
DOX injection resulted in significant increases in cardiac enzymes, inflammatory cytokines, and oxidative stress markers and decreased antioxidant levels. These indicate its cardiotoxic effect. Treatment with Illicium verum extract before injection improved the aforementioned biochemical parameters in a dose-dependent manner. The highest protective effect was observed in the 200 mg/kg extract group. This treatment had lower levels of cardiac injury markers and inflammatory mediators compared to the DOX group. In the extract-treated groups, myocardial injury was reduced, cellular degeneration was reduced, and tissue structure was improved.
Conclusion
Based on the results of this study, it can be suggested that Illicium verum extract can have significant cardioprotective effects against DOX-induced cardiotoxicity. These positive effects may be due to its antioxidant and anti-inflammatory properties. Therefore, it is hoped that Illicium verum can be used to reduce cardiac damage associated with doxorubicin treatment. However, further studies on a larger scale are needed to draw definitive conclusions.

Keywords

References

Abdulkareem Aljumaily, S. A., Demir, M., Elbe, H., Yigitturk, G., Bicer, Y., & Altinoz, E. (2021). Antioxidant, anti-inflammatory, and anti-apoptotic effects of crocin against doxorubicin-induced myocardial toxicity in rats. Environmental Science and Pollution Research, 28(46), 65802–65813. https://doi.org/10.1007/s11356-021-15409-w
Al-Amir, H., Janabi, A., & Hadi, N. R. (2023). Ameliorative effect of nebivolol in doxorubicin-induced cardiotoxicity. Journal of Medicine and Life, 16(9), 1357–1363. https://doi.org/10.25122/jml-2023-0090
Alhazzani, K., Alotaibi, M. R., Alotaibi, F. N., Aljerian, K., As Sobeai, H. M., Alhoshani, A. R., Alanazi, A. Z., Alanazi, W. A., & Alswayyed, M. (2021). Protective effect of valsartan against doxorubicin-induced cardiotoxicity: Histopathology and metabolomics in vivo study. Journal of Biochemical and Molecular Toxicology, 35(9), Article e22842. https://doi.org/10.1002/jbt.22842
Ali, L. H., & Alkarbolii, M. M. (2024). Evaluation of the efficacy of Cordia myxa fruit on ISO-induced cardiotoxicity in male albino rats. Tikrit Journal for Agricultural Sciences, 24(4), 220–234. https://doi.org/10.25130/tjas.24.4.18
Amirteymoori, E., Khezri, A., Dayani, O., Mohammadabadi, M., Khorasani, S., Mousaie, A., & Kazemi-Bonchenari, M. (2021). Effects of linseed processing method (ground versus extruded) and dietary crude protein content on performance, digestibility, ruminal fermentation pattern, and rumen protozoa population in growing lambs. Italian Journal of Animal Science, 20(1), 1506–1517. https://doi.org/10.1080/1828051X.2021.1984324
Archer, S. (1993). Measurement of nitric oxide in biological models. FASEB Journal, 7(2), 349–360. https://doi.org/10.1096/fasebj.7.2.8440411
Avagimyan, A., Pogosova, N., Kakturskiy, L., Sheibani, M., Challa, A., Kogan, E., Fogacci, F., Mikhaleva, L., Vandysheva, R., Yakubovskaya, M., Faggiano, A., Carugo, S., Urazova, O., Jahanbin, B., Lesovaya, E., Polana, S., Kirsanov, K., Sattar, Y., Trofimenko, A., Demura, T., Saghazadeh, A., Koliakos, G., Shafie, D., Alizadehasl, A., Cicero, A., Costabel, J. P., Biondi-Zoccai, G., Ottaviani, G., & Sarrafzadegan, N. (2024). Doxorubicin-related cardiotoxicity: Review of fundamental pathways of cardiovascular system injury. Cardiovascular Pathology, 73, Article 107683. https://doi.org/10.1016/j.carpath.2024.107683
Bancroft, J. D., & Gamble, M. (2008). Theory and practice of histological techniques (6th ed.). Elsevier Health Sciences.
Bhutani, V., Varzideh, F., Wilson, S., Kansakar, U., Jankauskas, S. S., & Santulli, G. (2025). Doxorubicin-induced cardiotoxicity: A comprehensive update. Journal of Cardiovascular Development and Disease, 12(6), Article 207. https://doi.org/10.3390/jcdd12060207
Cengiz, O., Baran, M., Balcioglu, E., Suna, P. A., Bilgici, P., Goktepe, O., Onder, G. O., Goc, R., & Yay, A. (2021). Use of selenium to ameliorate doxorubicin induced hepatotoxicity by targeting pro-inflammatory cytokines. Biotechnic & Histochemistry, 96(1), 67–75. https://doi.org/10.1080/10520295.2020.1760353
Chaulin, A. M. (2023). The essential strategies to mitigate cardiotoxicity caused by doxorubicin. Life, 13(11), Article 2148. https://doi.org/10.3390/life13112148
Cheah, I. K., Tang, R. M. Y., Wang, X., Sachaphibulkij, K., Chong, S. Y., Lim, L. H. K., Wang, J. W., & Halliwell, B. (2023). Protection against doxorubicin-induced cardiotoxicity by ergothioneine. Antioxidants, 12(2), Article 320. https://doi.org/10.3390/antiox12020320
Eisvand, F., Imenshahidi, M., Ghasemzadeh Rahbardar, M., Tabatabaei Yazdi, S. A., Rameshrad, M., Razavi, B. M., & Hosseinzadeh, H. (2022). Cardioprotective effects of alpha-mangostin on doxorubicin-induced cardiotoxicity in rats. Phytotherapy Research, 36(1), 506–524. https://doi.org/10.1002/ptr.7356
Hissin, P. J., & Hilf, R. (1976). A fluorometric method for determination of oxidized and reduced glutathione in tissues. Analytical Biochemistry, 74(1), 214–226. https://doi.org/10.1016/0003-2697(76)90326-2
Iftikhar, N., Hussain, A. I., Kamal, G. M., Manzoor, S., Fatima, T., Alswailmi, F. K., Ahmad, A., Alsuwayt, B., & Abdullah Alnasser, S. M. (2022). Antioxidant, anti-obesity, and hypolipidemic effects of polyphenol rich star anise (Illicium verum) tea in high-fat-sugar diet-induced obesity rat model. Antioxidants, 11(11), Article 2240. https://doi.org/10.3390/antiox11112240
Karim, S., Pawar, R. S., Bagre, A., & Gaurav, A. (2023). Formulation, development and bioavailability profiling of Illicium verum (methanolic fraction). European Journal of Biomedical and Pharmaceutical Sciences, 10(7), 194–201. https://www.ejbps.com/ejbps/abstract_id/9538
Khan, H. N., Rasheed, S., Choudhary, M. I., & Ahmed, N. (2022). Anti-glycation properties of Illicium verum Hook. f. fruit in-vitro and in a diabetic rat model. BMC Complementary Medicine and Therapies, 22, Article 79. https://doi.org/10.1186/s12906-022-03550-z
Khezri, A., Shafabakhsh, H., Alizadeh, A., Mohammadabadi, M., & Shakeri, M. (2025). Effects of Encapsulated Mixtures of Plant Essential Oils and Organic Acids as an Alternative to Antibiotic Growth Promoters on Humoral Immune Response and Expression of Interleukin-4 and Interferon-Gamma Genes in Broilers. Journal of Poultry Sciences and Avian Diseases 3(3), 12-19. https://doi.org/10.61838/kman.jpsad.3.3.3  
Li, W., Wu, Z., Xia, Y., Tan, J., Zhao, H., Chen, S., Li, Y., Tang, H., Wang, G., Zhang, Y. (2022). Antiviral and antioxidant components from the fruits of Illicium verum Hook.f. (Chinese star anise). Journal of Agricultural and Food Chemistry, 70(12), 3697–3707. https://doi.org/10.1021/acs.jafc.1c08376
Lin, X., Wu, G., Wang, S., & Huang, J. (2023). Bibliometric and visual analysis of doxorubicin-induced cardiotoxicity. Frontiers in Pharmacology, 14, Article 1255158. https://doi.org/10.3389/fphar.2023.1255158
Linders, A. N., Dias, I. B., López Fernández, T., Tocchetti, C. G., Bomer, N., & Van der Meer, P. (2024). A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging. npj Aging, 10, Article 9. https://doi.org/10.1038/s41514-024-00135-7
Majali, I. S. (2022). Antioxidant and anti-inflammatory activity of star anise (Illicium verum) in murine model. Biomedical and Pharmacology Journal, 15(2), 1097–1108. https://doi.org/10.13005/bpj/2445
Mohamed, H. K., Mobasher, M. A., Ebiya, R. A., Hassen, M. T., Hagag, H. M., El-Sayed, R., Abdel-Ghany, S., Said, M. M., & Awad, N. S. (2022). Anti-inflammatory, anti-apoptotic, and antioxidant roles of honey, royal jelly, and propolis in suppressing nephrotoxicity induced by doxorubicin in male albino rats. Antioxidants, 11(5), Article 1029. https://doi.org/10.3390/antiox11051029
Mohammadabadi, M., Afsharmanesh, M., Khezri, A., Kheyrodin, H., Babenko, O., Borshch, O. O., Kalashnyk, O., Nechyporenko, O., Afanasenko, V., Slynko, V., & Usenko, S. (2025). Effect of mealworm on GBP4L gene expression in the spleen tissue of Ross broiler chickens. Agricultural Biotechnology Journal, 17(2), 343–360. https://doi.org/10.22103/jab.2025.25277.1714
Mohammadabadi, M., Babenko, O., Borshch, O. O., Kalashnyk, O., Ievstafiieva, Y., & Buchkovska, V. (2024). Measurement of the relative expression pattern of the UCP2 gene in different tissues of the Raini Cashmere goat. Agricultural Biotechnology Journal, 16(3), 317–332. https://doi.org/10.22103/jab.2024.24337.1627
Mohammadabadi, M., Golkar, A., & Askari Hesni, M. (2023). The effect of fennel (Foeniculum vulgare) on insulin-like growth factor 1 gene expression in the rumen tissue of Kermani sheep. Agricultural Biotechnology Journal, 15(4), 239–256. https://doi.org/10.22103/jab.2023.22647.1530
Mohammadabadi, M., Shaban Jorjandy, D., Arabpoor Raghabadi, Z., Abareghi, F., Sasan, H. A., & Bordbar, F. (2022). The role of fennel on DLK1 gene expression in sheep heart tissue. Agricultural Biotechnology Journal, 14(2), 155–170. https://doi.org/10.22103/jab.2022.19402.1399
Mohanasundari, L., Brindha Devi, G. B., Saiyad Musthafa, M., & Madhavi, M. (2022). Effects of Illicium verum Hook. f. (Chinese herb) enriched diet on growth performance, immune response and disease resistance in Catla catla [Hamilton] fingerlings against Aeromonas hydrophila. Fish & Shellfish Immunology, 127, 455–462. https://doi.org/10.1016/j.fsi.2022.06.050
Mulla, S., & Patil, S. B. (2025). A review on phytopharmacological profile of Illicium verum Hook. f. Journal of Pharma Insights and Research, 3, 66–74. https://doi.org/10.69613/rkjcsh66
Naderi, Y., Khosraviani, S., Nasiri, S., Hajiaghaei, F., Aali, E., Jamialahmadi, T., Banach, M., & Sahebkar, A. (2023). Cardioprotective effects of minocycline against doxorubicin-induced cardiotoxicity. Biomedicine & Pharmacotherapy, 158, Article 114055. https://doi.org/10.1016/j.biopha.2022.114055
Patra, J. K., Das, G., Bose, S., Banerjee, S., Vishnuprasad, C. N., Del Pilar Rodriguez-Torres, M., & Shin, H. S. (2020). Star anise (Illicium verum): Chemical compounds, antiviral properties, and clinical relevance. Phytotherapy Research, 34(6), 1248–1267. https://doi.org/10.1002/ptr.6614
Rawat, P. S., Jaiswal, A., Khurana, A., Bhatti, J. S., & Navik, U. (2021). Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomedicine & Pharmacotherapy, 139, Article 111708. https://doi.org/10.1016/j.biopha.2021.111708
Roudbar, M. A., Mohammadabadi, M. R., & Salmani, V. (2015). Epigenetics: A new challenge in animal breeding. Genetics in the Third Millennium, 12(4), 3736–3751. https://www.researchgate.net/publication/281109256_Epigenetics_A_new_Challenge_In_Animal_Breeding
Safaei, S. M. H., Mohammadabadi, M., Moradi, B., Kalashnyk, O., Klopenko, N., Babenko, O., Borshch, O. O., & Afanasenko, V. (2025). Corrigendum: Role of fennel (Foeniculum vulgare) seed powder in increasing testosterone and IGF1 gene expression in the testis of lamb. Gene Expression, 24(4), Article e00020C. https://doi.org/10.14218/GE.2023.00020C
Sharafan, M., Jafernik, K., Ekiert, H., Kubica, P., Kocjan, R., Blicharska, E., & Szopa, A. (2022). Illicium verum (star anise) and trans-anethole as valuable raw materials for medicinal and cosmetic applications. Molecules, 27(3), Article 650. https://doi.org/10.3390/molecules27030650
Sies, H., Belousov, V. V., Chandel, N. S., Davies, M. J., Jones, D. P., Mann, G. E., Murphy, M. P., Yamamoto, M., Winterbourn, C., et al. (2022). Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nature Reviews Molecular Cell Biology, 23(7), 499–515. https://doi.org/10.1038/s41580-022-00456-z
Singh, S., & Verma, R. (2024). Comprehensive review on pharmacological potential of Illicium verum, Chinese herb. Pharmacological Research - Modern Chinese Medicine, 10, Article 100411. https://doi.org/10.1016/j.prmcm.2024.100411
Syahputra, R. A., Harahap, U., Dalimunthe, A., Nasution, M. P., & Satria, D. (2022). The role of flavonoids as a cardioprotective strategy against doxorubicin-induced cardiotoxicity: A review. Molecules, 27(4), Article 1320. https://doi.org/10.3390/molecules27041320
Tuseef, H., Raza, M. L., & Assad, T. (2021). Comparative evaluation of analgesic, antipyretic & anti-inflammatory effects of various extracts of dried fruit of Illicium verum Hook. f. (star anise) in rodents. Walailak Journal of Science and Technology, 18, Article 9456. https://doi.org/10.48048/wjst.2021.9456
Vahabzadeh, M., Chamani, M. M., Dayani, O., Sadeghi, A. A., & Mohammadabadi, M. R. (2021). Effects of sweet marjoram (Origanum majorana) powder on growth performance, nutrient digestibility, rumen fermentation, meat quality and humoral immune response in fattening lambs. Iranian Journal of Applied Animal Science, 11(3), 567–576. https://sanad.iau.ir/Journal/ijas/Article/1023983
Vahabzadeh, M., Chamani, M., Dayani, O., & Sadeghi, A. A. (2020). Effect of Origanum majorana leaf (sweet marjoram) feeding on lamb’s growth, carcass characteristics, and blood biochemical parameters. Small Ruminant Research, 192, Article 106233. https://doi.org/10.1016/j.smallrumres.2020.106233
Wu, L., Wang, L., Du, Y., Zhang, Y., & Ren, J. (2023). Mitochondrial quality control mechanisms as therapeutic targets in doxorubicin-induced cardiotoxicity. Trends in Pharmacological Sciences, 44(1), 34–49. https://doi.org/10.1016/j.tips.2022.10.003
Yang, E. C., Hsieh, Y. Y., & Chuang, L. Y. (2021). Comparison of the phytochemical composition and antibacterial activities of the various extracts from leaves and twigs of Illicium verum. Molecules, 26(13), Article 3909. https://doi.org/10.3390/molecules26133909
Yilmaz, S., Kaya, E., Yonar, H., & Mendil, A. S. (2022). Doxorubicin-induced oxidative stress injury: The protective effect of kumiss on cardiotoxicity. Journal of the Hellenic Veterinary Medical Society, 73(4), 4545–4558. https://doi.org/10.12681/jhvms.27822
Zhu, L., Luo, Y., Xiao, J., Hao, E., Wei, J., Zhao, J., Yao, C., Wang, Y., & Luo, H. (2024). Star anise (Illicium verum Hook. f.): Dual therapeutic and nutritional potential in food and medicine. Acupuncture and Herbal Medicine, 4(4), 563–587. https://doi.org/10.1097/HM9.0000000000000134    
 
Agricultural Biotechnology Journal
Volume 18, Issue 3
June 2026
Pages 155-176

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