The Use of Panax Ginseng to Reduce the Cardiotoxicity of Doxorubicin and Study its Effect on Modulating Oxidative Stress, Inflammatory, and Apoptosis Pathways

Hany Akeel Al-Hussaniy; Hayder M. Al-Kuraishy; Abdul-Ghaffar A. Abdulameer

doi:10.3889/oamjms.2022.9479

Authors

Hany Akeel Al-Hussaniy Department of Pharmacology, College of Medicine, Baghdad University, Alnukhaba University College, Baghdad, Iraq
Hayder M. Al-Kuraishy Department of Pharmacology, College of Medicine, University of Almustansria, Baghdad, Iraq
Abdul-Ghaffar A. Abdulameer Department of Pharmacy, Ministry of Health, Baghdad, Iraq

DOI:

https://doi.org/10.3889/oamjms.2022.9479

Keywords:

Panax ginseng, Free radical, Apoptotic pathways, Doxorubicin-induced cardiotoxicity

Abstract

BACKGROUND: Doxorubicin (DOX) is a broad-spectrum anti-cancer drug that is used to treat a variety of cancers, including blood cancers such as leukemia and solid tissue cancers. However, its use some time limited because of its cardiotoxicity.

OBJECTIVE: The objective of the study was to determine the cardioprotective effect of ginseng in the case of cardiotoxicity caused by doxorubicin therapy.

Methods: Thirty experimental animals (male Sprague Wistar rats) were used in this research and they were separated into three groups: Rats in Group I (n# = 10) were given distilled water plus normal saline, rats in Group II (n# = 10) were given distilled water plus doxorubicin, and rats in Group III (n# = 10) were given Panax ginseng plus doxorubicin. Serum concentration, malondialdehyde (MDA), glutathione reductase (GSH), lipid peroxidase (LPO), TNF (ng/L), cardiac troponin (ng/L), brain natriuretic peptide BNP(g/L), and caspase-3 (pmol/L) levels were measured in all groups.

RESULTS: Doxorubicin caused substantial cardiotoxicity as a result of a significant increase in the elevation of cTnI to 40.09 ± 6.67 (ng/L). In addition, MDA, LPO, TNF-α, and caspase-3 levels were increased in doxorubicin group compared to the control group p < 0.05. Panax ginseng reduced cardiac troponin (cTnI) However, its effect on reduction of BNP levels insignificantly compared to the doxorubicin group p = 0.06. Panax ginseng reduced LPO and MDA and raised the antioxidant potential biomarker GSH significantly compared to the doxorubicin group p < 0.05. Panax ginseng significantly reduced inflammatory (TNF-α) and apoptotic (caspase-3) biomarkers when compared to the doxorubicin group.

CONCLUSIONS: According to the findings of this study, Panax ginseng suppresses reactive oxygen species and inflammatory and apoptotic pathways in experimental rats, thereby preventing doxorubicin-induced cardiovascular events.

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References

Alkuraishy HM, Al-Gareeb AI, Al-hussaniy HA. Doxorubicin induced cardiotoxicity: Molecular mechanism and protection by conventional drugs and natural products. Int J Clin Oncol Cancer Res. 2017;2:31-44.

Alkuraishy H, Khaleel K, Mohammed M. Significant attenuation and amelioration effects of labetalol in doxorubicin induced cardiotoxicity: An animal model study. J Cardiovasc Surg. 2015;3(2):25-29. https://doi.org/10.5455/jcvs.2015321 DOI: https://doi.org/10.5455/jcvs.2015321

Alkuraishy HM, Al-Gareeb AI. Advances and prospects of nicardipine effects in attenuation of hydroxy-daunorubicin induced acute cardiotoxicity in rats. Adv Biomed Pharm. 2015;2:274-82. https://doi.org/10.19046/abp.v02i06.05 DOI: https://doi.org/10.19046/abp.v02i06.05

Wang Z, Wang J, Xie R, Liu R, Lu Y. Mitochondria-derived reactive oxygen species play an important role in doxorubicin-induced platelet apoptosis. Int J Mol Sci. 2015;16(5):11087-100. https://doi.org/10.3390/ijms160511087 PMid:25988386 DOI: https://doi.org/10.3390/ijms160511087

Mnatsakanyan N, Beutner G, Porter GA, Alavian KN, Jonas EA. Physiological roles of the mitochondrial permeability transition pore. J Bioenerg Biomemb. 2017;49(1):13-25. https://doi.org/10.1007/s10863-016-9652-1 PMid:26868013 DOI: https://doi.org/10.1007/s10863-016-9652-1

Al-Zubaidi RF, Al-Shawi NN. Impact of two doses of Vitamin K2 (menaquinone-7) on doxorubicin-induced hepatotoxicity in rats. Iraqi J Pharm Sci. 2017;26(2):22-8. https://doi.org/10.31351/vol26iss2pp22-28 DOI: https://doi.org/10.31351/vol26iss2pp22-28

Ganatra S, Nohria A, Shah S, Groarke JD, Sharma A, Venesy D, et al. Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: A consecutive case series. Cardiooncology. 2019;5(1):1-12. https://doi.org/10.1186/s40959-019-0036-7 DOI: https://doi.org/10.1186/s40959-019-0036-7

Al-Kuraishy H, Al-Gareeb A. Comparison of deferasirox and deferoxamine effects on iron overload and immunological changes in patients with blood transfusion-dependent β-thalassemia. Asian J Transfus Sci. 2017;11(1):13-7. https://doi.org/10.4103/0973-6247.200768 DOI: https://doi.org/10.4103/0973-6247.200768

Abdulrazzaq MH. Protective effect of benfotiamine against doxorubicin-induced cardiotoxicity in rabbits. Iraqi J Pharm Sci. 2007;16(1):14-7. https://doi.org/10.31351/vol16iss1pp14-17 DOI: https://doi.org/10.31351/vol16iss1pp14-17

Chung SI, Kang MY, Lee SC. In vitro and in vivo antioxidant activity of aged ginseng (Panax ginseng). Prev Nutr Food Sci. 2016;21(1):24-30. https://doi.org/10.3746/pnf.2016.21.1.24 PMid:27069902 DOI: https://doi.org/10.3746/pnf.2016.21.1.24

Al-Hussaniy HA, Alburghaif AH, Naji MA. Leptin hormone and its effectiveness in reproduction, metabolism, immunity, diabetes, hopes and ambitions. J Med Life. 2021;14(5):600-5. https://doi.org/10.25122/jml-2021-0153 PMid:35027962 DOI: https://doi.org/10.25122/jml-2021-0153

Jang YJ, Lee D, Hossain MA, Aravinthan A, Kang CW, Kim NS, et al. Korean Red Ginseng enhances cardiac hemodynamics on doxorubicin-induced toxicity in rats. J Ginseng Res. 2020;44(3):483-9. https://doi.org/10.1016/j.jgr.2019.03.002 PMid:32372870 DOI: https://doi.org/10.1016/j.jgr.2019.03.002

Al-Geam MA, Al-Shawi NN. Effects of Vitamin E and Q10 supplementation against doxorubicin-induced neurotoxicity in rats. Iraqi J Pharm Sci. 2018;11:24-31. https://doi.org/10.31351/vol27iss2pp24-31 DOI: https://doi.org/10.31351/vol27iss2pp24-31

Al-hassany HA, Albu-rghaif AH, A. Naji M. Tumor diagnosis by genetic markers protein P-53, p16, C-MYC, N-MYC, protein K-Ras, and gene her-2 Neu is this possible? Pak J Med Health Sci. 2021;15(8):2350-4. https://doi.org/10.53350/pjmhs211582350 DOI: https://doi.org/10.53350/pjmhs211582350

ALZobaidy MA, AlbuRghaif AH, Alhasany HA, Naji MA. Angiotensin-Converting Enzyme Inhibitors May Increase Risk of Severe COVID-19 Infection. Annals of the Romanian Society for Cell Biology. 2021;25(6):17843-9 PMid:23717054

Al-khafaf A, Ismail HK, Alsaidya A. Histopathological effects of experimental exposure to lead on nervous system in albino female rats. Iraqi J Vet Sci. 2021;35(1):45-8. https://doi.org/10.5142/jgr.2011.35.2.129 DOI: https://doi.org/10.33899/ijvs.2019.126248.1273

Liu TP, Liu IM, Cheng JT. Improvement of insulin resistance by Panax ginseng in fructose rich Chow fed RatsT. Horm Metab Res. 2005;37(3):146-51. https://doi.org/10.1055/s-2005-861299 PMid:15824968 DOI: https://doi.org/10.1055/s-2005-861299

Ridha DK, Al-Shawi NN. The impacts of graded doses of pyridoxine on the biomarkers, aspartate aminotransferase, lactate dehydrogenase and total antioxidant capacity in doxorubicin-induced cardiotoxicity in female rats. Iraqi J Pharm Sci. 2017;26:12-21. https://doi.org/10.31351/vol26iss2pp12-21 DOI: https://doi.org/10.31351/vol26iss2pp12-21

Al-Kuraishy HM, Al-Gareeb Ali I, Naji HA. Febuxostat modulates oxidative and apoptotic pathways in acute doxorubicin induced cardiotoxicity: An experimental animal model study. Asian J Pharm Clin. 2019;12(4):73-6. https://doi.org/10.22159/ajpcr.2019.v12i4.31162 DOI: https://doi.org/10.22159/ajpcr.2019.v12i4.31162

Kim JH, Yi YS, Kim MY, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res. 2017;41(4):435-43. https://doi.org/10.1016/j.jgr.2016.08.004 PMid:29021688 DOI: https://doi.org/10.1016/j.jgr.2016.08.004

Hasan HF. Effects of alcoholic extract of panax ginseng Seeds and Tamoxifen citrate drug on some fertility parameters and histopathological changes in testes of mice treated with doxorubicin. Kufa Journal For Veterinary Medical Science s. 2016;7(1) PMid:30662301

Sun X, Li C, Lu J. Protective effect of ginsenoside Rd against isoproterenol-induced myocardial infarction in Wistar rats. Trop J Pharm Res. 2019;18(1):93-100. https://doi.org/10.4314/tjpr.v18i1.14 DOI: https://doi.org/10.4314/tjpr.v18i1.14

Chen J, Liu GZ, Sun Q, Zhang F, Liu CY, Yuan L, et al. Protective effects of ginsenoside Rg3 on TNF-α-induced human nucleus pulposus cells through inhibiting NF-κB signaling pathway. Life Sci. 2019;216:1-9. https://doi.org/10.1016/j.lfs.2018.11.022 PMid:30428306 DOI: https://doi.org/10.1016/j.lfs.2018.11.022

Al-Hussaniy HA, Altalebi RR, Alburagheef A, Abdul-Amir AG. The use of PCR for respiratory virus detection on the diagnosis and treatment decision of respiratory tract infections in Iraq. J Pure Appl Microbiol. 2022;16(1):201-6. https://doi.org/10.22207/jpam.16.1.10 DOI: https://doi.org/10.22207/JPAM.16.1.10

Al-Jammas S, Al-Saraj A. The histological changes induced by Cytarabine on rabbits livers (with and without Vitamin E administration). Iraqi J Vet Sci. 2020;34(1):9-13. https://doi.org/10.33899/ijvs.2020.163564 DOI: https://doi.org/10.33899/ijvs.2020.163564

Al-Kuraishy HM, Al-Gareeb AI, Al-Hussaniy HA, Al-Harcan NAH, Alexiou A, Batiha GE. Neutrophil extracellular traps (NETs) and Covid- 19: A new frontiers for therapeutic modality. Int Immunopharmacol. 2022;104:108516. https://doi.org/10.1016/j.intimp.2021.108516 PMid:35032828 DOI: https://doi.org/10.1016/j.intimp.2021.108516