Interactive Effect of the Linum Usitatissimum Extracts and Exercise Rehabilitation on Aorta Endothelial and Heart Tissues Apoptosis Biomarkers

Document Type : Research Paper


1 Ph.D. Student, Department of Physical Education and Sport Sciences, Mahallat Branch, Islamic Azad University. Mahallat, Iran.

2 Professor, Department of Physical Education and Sport Sciences, Mahallat Branch, Islamic Azad University. Mahallat, Iran.

3 Assistant Professor, Department of Physical Education, Pardis Branch, Islamic Azad University, Pardis, Iran.


Introduction: As one of the most life-threatening illnesses, cardiovascular diseases are often discerned with a high apoptosis rate because of exposure to the high level of oxidative stresses. The present study has investigated the interaction of the Linum Usitatissimum (Lu) and aerobic exercise (Ae) on apoptosis of aortic endothelial and heart tissue in rats intoxicated by H2O2Methods: 56 male Albino Wistar rats were divided into 7 groups, included HC (Healthy Control), TC (Toxic-Control), Toxic-Lu1 (Received Lu, 5 mg/kg), Toxic-Lu2 (Received Lu, 10 mg/kg), Toxic-Ae (Received Aerobic Exercise), Toxic-Ae+Lu1, and Toxic-Ae+Lu2. Finally, the rats were sacrificed ethically, and the apoptotic biomarkers were measured in isolated aortic endothelial and heart tissues. Results: The interactive comparisons showed that the Ae and Lu and aerobic exercise had a significant interactive change on pro-apoptosis biomarkers. The BAX in aortic endothelial (P=0.0011) and heart (P=0.0007), caspase-3 in aortic endothelial (P=0.0006) and heart (P=0.0016), and Bcl-2 in aortic endothelial (P=0.0018) and heart (P=0.0016) have significant interactive changes. No significant independent effect was observed. Post hoc test showed that group Toxic-Ae+Lu2 have the most significant improvement compared to the TC group (P≤0.05). Conclusions: The simultaneous effect of Ae and Lu supplementation most effectively improved the apoptosis biomarkers and displayed potent cardioprotective effects compared to the singular administration of each intervention. Probably, the short rehabilitation period has caused non- significant independent changes. However, the interaction of Ae and Lu has shortened the treatment period.


1. Pfeffer CM, Singh AT. Apoptosis: a target for anticancer therapy. Int J Mol Sci. 2018;19(2):448.
2. Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochimica et Biophysica Acta (BBA). Mol Cell Res. 2016;1863(12):2977-92.
3. Sutrisno S, Sulistyorini C, Manungkalit EM, Winarsih L, Noorhamdani N, Winarsih S. The effect of genistein on TGF-β signal, dysregulation of apoptosis, cyclooxygenase-2 pathway, and NF-kB pathway in mice peritoneum of endometriosis model.  Middle East Fertil Soc J. 2017;22(4):295-9.
4. Wu H, Fu S, Zhao M, Lu L, Lu Q. Dysregulation of cell death and its epigenetic mechanisms in systemic lupus erythematosus. Molecules. 2017;22(1):30.
5. Hata AN, Engelman JA, Faber AC. The BCL2 family: key mediators of the apoptotic response to targeted anticancer therapeutics. Cancer Discov. 2015;5(5):475-87.
6. Siddiqui WA, Ahad A, Ahsan H. The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Arch Toxicol. 2015;89(3):289-317.
7. Nikkhoi SK, Rahbarizadeh F, Ahmadvand D. Oligo-clonal nanobodies as an innovative targeting agent for cancer therapy: new biology and novel targeting systems. Protein Expr Purif. 2017;129:115-21.
8. Sun Y, Liu W-Z, Liu T, Feng X, Yang N, Zhou H-F. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res. 2015;35(6):600-4.
9. Övey I, Naziroğlu M. Homocysteine and cytosolic GSH depletion induce apoptosis and oxidative toxicity through cytosolic calcium overload in the hippocampus of aged mice: involvement of TRPM2 and TRPV1 channels. Neuroscience. 2015;284:225-33.
10. Piao MJ, Ahn MJ, Kang KA, Ryu YS, Hyun YJ, Shilnikova K, et al. Particulate matter 2.5 damages skin cells by inducing oxidative stress, subcellular organelle dysfunction, and apoptosis. Arch Toxicol. 2018;92(6):2077-91.
11. Roslan J, Giribabu N, Karim K, Salleh N. Quercetin ameliorates oxidative stress, inflammation and apoptosis in the heart of streptozotocin-nicotinamide-induced adult male diabetic rats. Biomed Pharmacother. 2017;86:570-82.
12. Münzel T, Camici GG, Maack C, Bonetti NR, Fuster V, Kovacic JC. Impact of oxidative stress on the heart and vasculature: part 2 of a 3-part series. J Am Coll Cardiol. 2017;70(2):212-29.
13. Nikkhoi SK, Heydarzadeh H, Ranjbar S, Salimi F, Aghaeifard M, Alavian SM, et al. The evaluation and comparison of transcriptionally targeted noxa and puma killer genes to initiate apoptosis under cancer-specific promoter cxcr1 in hepatocarcinoma gene therapy. Hepat Mon. 2016;16(10).
14. Cheng Y-C, Sheen J-M, Hu WL, Hung Y-C. Polyphenols and oxidative stress in atherosclerosis-related ischemic heart disease and stroke. Oxid Med Cell Longev. 2017;2017.
15. Li Z-m, Xu S-w, Liu P-q. Salvia miltiorrhiza Burge (Danshen): A golden herbal medicine in cardiovascular therapeutics. Acta Pharmacol Sin. 2018;39(5):802-24.
16. Herchi W, AMMAR KB, Bouali I, Abdallah IB, Guetet A, Boukhchina S. Heating effects on physicochemical characteristics and antioxidant activity of flaxseed hull oil (Linum usitatissimum L). Food Sci Technol. 2016;36(1):97-102.
17. Ramesh M. Flax (Linum usitatissimum L.) fibre reinforced polymer composite materials: A review on preparation, properties and prospects. Prog Mater Sci. 2019;102:109-66.
18. Keykhasalar R, Tabrizi MH, Ardalan P, Khatamian N. The Apoptotic, Cytotoxic, and Antiangiogenic Impact of Linum usitatissimum Seed Essential Oil Nanoemulsions on the Human Ovarian Cancer Cell Line A2780. Nutr Cancer. 2020:1-9.
19. Huang G, Huang X, Liu M, Hua Y, Deng B, Jin W, et al. Secoisolariciresinol diglucoside prevents the oxidative stress-induced apoptosis of myocardial cells through activation of the JAK2/STAT3 signaling pathway.  Int J Mol Med. 2018;41(6):3570-6.
20. Hou T-t, Yang X-y, Xia P, Pan S, Liu J, Qi Z-p. Exercise promotes motor functional recovery in rats with corticospinal tract injury: antiapoptosis mechanism. Neural Regen Res. 2015;10(4):644.
21. Jafari A, Pourrazi H, Nikookheslat S, Baradaran B. Effect of exercise training on Bcl-2 and bax gene expression in the rat heart. Gene, Cell and Tissue. 2015;2(4):e32833.
22. Silva Jr SD, Jara ZP, Peres R, Lima LS, Scavone C, Montezano AC, et al. Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction. PloS one. 2017;12(12):e0189535.
23. Hyatt HW, Smuder AJ, Sollanek KJ, Morton AB, Roberts MD, Kavazis AN. Comparative changes in antioxidant enzymes and oxidative stress in cardiac, fast twitch and slow twitch skeletal muscles following endurance exercise training. Int J Physiol Pathophysiol Pharmacol. 2016;8(4):160.
24. Ormazabal V, Nair S, Elfeky O, Aguayo C, Salomon C, Zuñiga FA. Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol. 2018;17(1):122.
25. Brown MB, Neves E, Long G, Graber J, Gladish B, Wiseman A, et al. High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension. Am J Physiol Regul Integr Comp Physiol. 2017;312(2):R197-R210.
26. Santilli F, Guagnano M, Vazzana N, La Barba S, Davi G. Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach. Curr Med Chem. 2015;22(5):582-95.
27. Kim D-E, Kim B, Shin H-S, Kwon HJ, Park E-S. The protective effect of hispidin against hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblast cells through Akt/GSK-3β and ERK1/2 signaling pathway. Exp Cell Res. 2014;327(2):264-75.
28. Bao L, Avshalumov MV, Rice ME. Partial mitochondrial inhibition causes striatal dopamine release suppression and medium spiny neuron depolarization via H2O2 elevation, not ATP depletion. J Neurosci. 2005;25(43):10029-40.
29. Lee S-D, Shyu W-C, Cheng I-S, Kuo C-H, Chan Y-S, Lin Y-M, et al. Effects of exercise training on cardiac apoptosis in obese rats. Nutr Metab Cardiovasc Dis. 2013;23(6):566-73.
30. Ganguly R, Hasanally D, Stamenkovic A, Maddaford TG, Chaudhary R, Pierce GN, et al. Alpha linolenic acid decreases apoptosis and oxidized phospholipids in cardiomyocytes during ischemia/reperfusion. Mol Cell Biochem. 2018;437(1-2):163-75.
31. Dali S, Krouf D, Mellouk Z, Taleb-Dida N. Beneficial effects of linum usitatissimum L. on dyslipidemia, oxidative stress and inflammatory cytokines in hypercholesterolemic rats. Nutr Food Sci. 2019.
32. Jhala AJ, Hall LM. Flax (Linum usitatissimum L.): current uses and future applications. Aust J Basic Appl Sci. 2010;4(9):4304-12.
33. Shirvani H, Rahmati-Ahmadabad S. The combined effect of high intensity interval training and flaxseed oil supplement on cardioprotection: by UCP2, UCP3 and eNOS mRNA expression. J Maz Univ Med Sci. 2018;28(160):8-18.
34. Ghosh S, Banerjee S, Sil PC. The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update. Food Chem Toxicol. 2015;83:111-24.
35. Derbali A, Mnafgui K, Affes M, Derbali F, Hajji R, Gharsallah N, et al. Cardioprotective effect of linseed oil against isoproterenol-induced myocardial infarction in Wistar rats: a biochemical and electrocardiographic study. J Physiol Biochem. 2015;71(2):281-8.
36. Hasan ZA, AL-Saeed MH. Cardioprotective and Antilipidemic Role of Ocimum basilicum Seeds Oil and Linum usitatissimum Seeds Oil in Acute Myocardial Infarction Male Rabbits Induced by Isoproterenol. Basra J Vet Res. 2018;17(3).
Volume 9, Issue 3
September 2021
Pages 254-262
  • Receive Date: 23 April 2021
  • Revise Date: 06 August 2021
  • Accept Date: 07 August 2021
  • First Publish Date: 07 August 2021