Document Type : Original Article(s)


1 Airlangga University, Surabaya, Indonesia

2 Indonesia University, Jawa Barat, Indonesia


BACKGROUND: Oxidative stress caused by various components in cigarette smoke can induce endothelial dysfunction. Black cumin (Nigella sativa) has an oxidative stress inhibition capability by increasing antioxidant enzyme production and decreasing lipid peroxidation.
METHODS: This is an in vivo study with a post-test only design using Wistar rats as subjects. Rats were randomly assigned into five groups: negative control (NC) group without any treatment, positive control (PC) group exposed to cigarette smoke only, and treatment groups (T1, T2, and T3) which received exposure of cigarette smoke and administration of black cumin extract with doses of 0.3 g/kg BW/day (T1), 0.6 g/Kg BW/day (T2), and 1.2 g/kg BW/day (T3). After four weeks, samples were sacrificed with the aortas taken to measure superoxide dismutase (SOD)
activity and malondialdehyde (MDA) level.
RESULTS: A significant reduction in SOD activity (p=0.022) was found between the NC and PC groups but not in MDA level (p=0.394). SOD activity increased significantly in T2 when compared to PC (p=0.007). MDA levels significantly increased at T1 (p=0.002), T2 (p=0.005), and T3 (p=0.006) when compared to PC.
CONCLUSION: Black cumin ethanolic extract increased SOD activity in Wistar rats exposed to cigarette smoke. However, no reduce of MDA level was observed.


  1. Smiljic S. The clinical significance of endocardial endothelial dysfunction. Medicina (Kaunas). 2017 Dec;53(5):295–302.
  2. Nedeljkovic ZS, Gokce N, Loscalzo J. Mechanisms of oxidative stress and vascular dysfunction. Vol. 79, Postgraduate Medical Journal. 2003. p. 195–200.
  3. Syaputra A, Asni E, Malik Z, Ismawati. Histopatologi Arteri Koroner Rattus novergicus Strain Wistar Jantan pada Minggu ke-12 setelah Pemberian Diet Aterogenik. J Med FK. 2014;1(2).
  4. Kakadiya J, Jagdish M, Kakadiya L. Treatment of Atherosclerosis and Coronary Artery Disease - A Review. Newsl Jagdish Kakadiya. 2009;3:458–83.
  5. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019 Mar 5;139(10):e56–66.
  6. Zhang C, Xu X, Potter BJ, Wang W, Kuo L, Michael L, et al. TNF-alpha contributes to endothelial dysfunction in ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):475–80.
  7. Münzel T, Gori T, Bruno RM, Taddei S. Is oxidative stress a therapeutic target in cardiovascular disease? Eur Heart J. 2010 Nov;31(22):2741–8.
  8. Daiber A, Steven S, Weber A, Shuvaev V V., Muzykantov VR, Laher I, et al. Targeting vascular (endothelial) dysfunction. Vol. 174, British Journal of Pharmacology. John Wiley and Sons Inc.; 2017. p. 1591–619.
  9. Kazemi M. Phytochemical Composition, Antioxidant, Anti-inflammatory and Antimicrobial Activity of Nigella sativa L. Essential Oil. J Essent Oil-Bearing Plants. 2014 Sep 3;17(5):1002–11.
  10. Ali SS, Ayuob NN, Al Ansary AK, Soluman ER. Antioxidants protect against increased risk of atherosclerosis induced by exposure to cigarette smoke: Histological and biochemical study. Saudi J Biol Sci. 2012;19(3):291–301.
  11. Jaldin RG, Castardelli É, Perobelli JE, Yoshida WB, De Castro Rodrigues A, Sequeira JL, et al. Morphologic and biomechanical changes of thoracic and abdominal aorta in a rat model of cigarette smoke exposure. Ann Vasc Surg. 2013;27(6):791– 800.
  12. Al-Saleh IA, Billedo G, El-Doush II. Levels of selenium, Dl-α-tocopherol, Dl-γ-tocopherol, alltrans-retinol, thymoquinone and thymol in different brands of Nigella sativa seeds. J Food Compos Anal. 2006 Mar;19(2–3):167–75.
  13. Hadad GM, Salam RAA, Soliman RM, Mesbah MK. High-performance liquid chromatography quantification of principal antioxidants in black seed (Nigella sativa L.) phytopharmaceuticals. J AOAC Int. 95(4):1043–7.
  14. Velho-Pereira RM, Barhate CR, Kulkarni SR, Jagtap AG. Validated high-performance thin-layer chromatographic method for the quantification of thymoquinone in Nigella Sativa extracts and formulations. Phytochem Anal. 2011;22(4):367–73.
  15. Koshak AE, Yousif NM, Fiebich BL, Koshak EA, Heinrich M. Comparative immunomodulatory activity of Nigella sativa L. preparations on proinflammatory mediators: A focus on asthma. Front Pharmacol. 2018;9(OCT):1–11.

16.Ichiki T. Collaboration between smokers and tobacco in endothelial dysfunction. Cardiovascular Research. 2011 Jun 1;90(3):395–6.

17.Carnevale R, Nocella C, Cammisotto V, Bartimoccia S, Monticolo R, D’Amico A, et al. Antioxidant activity from extra virgin olive oil via inhibition of hydrogen peroxide-mediated NADPH-oxidase 2 activation. Nutrition. 2018 Nov 1;55–56:36–40.

  1. Özkol H, Tülüce Y, Koyuncu I. Subacute effect of cigarette smoke exposure in rats: Protection by pot marigold (Calendula officinalis L.) extract. Toxicol Ind Health. 2012;28(1):3–9.
  2. Ramesh T, Sureka C, Bhuvana S, Begum VH. Oxidative stress in the brain of cigarette smoke-induced noxiousness: neuroprotective role of Sesbania grandiflora. Metab Brain Dis. 2015;30(2):573–82.
  3. Selim AO, Gouda ZA, Selim SA. An experimental study of a rat model of emphysema induced by cigarette smoke exposure and the effect of Survanta therapy. Ann Anat. 2017 May 1;211:69–77.
  4. Pasupathi P, Saravanan G, Farook J. Oxidative Stress Bio Markers and Antioxidant Status in Cigarette Smokers Compared to Nonsmokers. J Pharm Sci Res. 2009;1(2):55–62.
  5. PO M, CC O, CO O, GO C, NC I, SI O, et al. Assessment of Superoxide dismutase activity and total antioxidant capacity in adult male cigarette smokers in Nnewi metropolis, Nigeria. J Med Res. 2017 Feb;3(1):23–6.
  6. Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Vol. 2014, Oxidative Medicine and Cellular Longevity. Landes Bioscience; 2014. p. 1–31.
  7. Hussain T, Al-Attas OS, Alamery S, Ahmed M, Odeibat HAM, Alrokayan S. The plant flavonoid, fisetin alleviates cigarette smoke-induced oxidative stress, and inflammation in Wistar rat lungs. J Food Biochem. 2019;43(8):1–11.
  8. Lin L, Yin Y, Hou G, Han D, Kang J, Wang Q. Ursolic acid attenuates cigarette smoke-induced emphysema in rats by regulating PERK and Nrf2 pathways. Pulm Pharmacol Ther. 2017 Jun;44:111–21.
  9. Huang YC, Chin CC, Chen CS, Shindel AW, Ho DR, Lin CS, et al. Chronic cigarette smoking impairs erectile function through increased oxidative stress and apoptosis, decreased nNOS, endothelial and smooth muscle contents in a rat model. PLoS One. 2015;10(10):1–13.
  10. Chuang YC, Wu MS, Su YK, Fang KM. Effects of olmesartan on arterial stiffness in rats with chronic renal failure. Cardiovasc Diabetol. 2012;11(1):1.
  11. Wei Q, Ren X, Jiang Y, Jin H, Liu N, Li J. Advanced glycation end products accelerate rat vascular calcification through RAGE/oxidative stress. BMC Cardiovasc Disord. 2013;13(1):1.
  12. Al-Seeni MN, El Rabey HA, Zamzami MA, Alnefayee AM. The hepatoprotective activity of olive oil and Nigella sativa oil against CCl4 induced hepatotoxicity in male rats. BMC Complement Altern Med. 2016 Nov 4;16(1).
  13. Abdelmeguid NE, Fakhoury R, Kamal SM, Al Wafai RJ. Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic β-cells of streptozotocin-induced diabetic rats. J Diabetes. 2010 Dec;2(4):256–66.
  14. Rahman M, Yang DK, Kim GB, Lee SJ, Kim SJ. Nigella sativa seed extract attenuates the fatigue induced by exhaustive swimming in rats. Biomed Reports. 2017 Apr 1;6(4):468–74.
  15. Koka PS, Mondal D, Schultz M, Abdel-Mageed AB, Agrawal KC. Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells: role of reactive oxygen species. Exp Biol Med. 2010 Jun 1;235(6):751–60.
  16. Khader M, Bresgen N, Eckl PM. In vitro toxicological properties of thymoquinone. Food Chem Toxicol. 2009 Jan;47(1):129–33.
  17. Rooney S, Ryan MF. Modes of action of alphahederin and thymoquinone, active constituents of Nigella sativa, against HEp-2 cancer cells. Anticancer Res. 2005 Nov;25(6 B):4255–9.
  18. Kaleem M, Kirmani D, Asif M, Ahmed Q, Bano B. Biochemical effects of Nigella sativa L seeds in diabetic rats. Indian J Exp Biol. 2006 Sep;44(9):745– 8.
  19. Abbasnezhad A, Hayatdavoudi P, Niazmand S, Mahmoudabady M. The effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in hippocampus of STZ-induced diabetic rats. Avicenna J phytomedicine. 5(4):333–40.
  20. Pourghassem-Gargari B, Ebrahimzadeh-Attary V, Rafraf M, Gorbani A. Effect of dietary supplementation with Nigella sativa L. on serum lipid profile, lipid peroxidation and antioxidant defense system in hyperlipidemic rabbits. J Med Plants Res. 2009;3(10):815–21.
  21. Dudda A, Spiteller G, Kobelt F. Lipid oxidation products in ischemic porcine heart tissue. Chem Phys Lipids. 1996 Jul 30;82(1):39–51.

39.Jira W, Spiteller G, Carson W, Schramm A. Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients. Chem Phys Lipids. 1997 Jan;91(1):1–11.

  1. DiNicolantonio JJ, O’Keefe JH. Good Fats versus Bad Fats: A Comparison of Fatty Acids in the Promotion of Insulin Resistance, Inflammation, and Obesity. Mo Med. 2017;114(4):303–7.
  2. Angelia SR, Manikam NRM, Lubis AMT, Siagian C, Mudjihartini N. Association Between the Ratio of Omega-6/Omega-3 Fatty Acids Intake to Plasma Malondialdehyde Level in Patients with Knee Osteoarthritis. IOP Conf Ser Earth Environ Sci. 2019;217:1–6.