European Journal of Nutrition

, Volume 48, Issue 4, pp 235–242 | Cite as

Methanolic extract of onion (Allium cepa) attenuates ischemia/hypoxia-induced apoptosis in cardiomyocytes via antioxidant effect

  • Sok Park
  • Mi-Young Kim
  • Dong Ha Lee
  • Soo Hwan Lee
  • Eun Joo Baik
  • Chang-Hyun Moon
  • Se Won Park
  • Eun Young Ko
  • Sei-Ryang Oh
  • Yi-Sook JungEmail author
Original Contribution



Although there is growing awareness of the beneficial potential of onion intake to lower the risk of cardiovascular disease, there is little information about the effect of onion on ischemic heart injury, one of the most common cardiovascular diseases.

Aim of the study

This study investigates the effect of the methanol-soluble extract of onion on ischemic injury in heart-derived H9c2 cells in vitro and in rat hearts in vivo. The underlying mechanism is also investigated.


To evaluate the effect of onion on ischemia-induced cell death, LDH release and TUNEL-positivity were assessed in H9c2 cells, and the infarct size was measured in a myocardial infarct model. To investigate the mechanism of the cardioprotection by onion, the reactive oxygen species (ROS) level and the mitochondrial membrane potential (ΔΨm) were measured using an imaging technique; the caspase-3 activity was assayed, and Western blotting was performed to examine cytochrome c release in H9c2 cells.


The methanolic extract of onion had a preventive effect on ischemia/hypoxia-induced apoptotic death in H9c2 cells in vitro and in rat heart in vivo. The onion extract (0.05 g/ml) inhibited the elevation of the ROS, mitochondrial membrane depolarization, cytochrome c release and caspase-3 activation during hypoxia in H9c2 cells. In the in vivo rat myocardial infarction model, onion extract (10 g/kg) significantly reduced the infarct size, the apoptotic cell death of the heart and the plasma MDA level.


In conclusion, the results of this study suggest that the methanolic extract of onion attenuates ischemia/hypoxia-induced apoptosis in heart-derived H9c2 cells in vitro and in rat hearts in vivo, through, at least in part, an antioxidant effect.


Onion extract Antioxidant Cardioprotection Ischemic injury Apoptosis 



This study was supported by Technology Development Program for Agriculture and Forestry, Ministry for Agriculture, Forestry and Fisheries, and by “Specific Joint Agricultural Research-promoting Projects (20080401-033-302-001-02-00)”, RDA, Republic of Korea. This work was also supported by (2004) grant from “Department of Medical Sciences, The Graduate School, Ajou University”, and by a grant (CBM32-B3003-01-02-00) from the center for Biological Modulators of the 21st Century Frontier R&D Program of the Ministry of Science and Technology.


  1. 1.
    Buja LM (2005) Myocardial ischemia and reperfusion injury. Cardiovasc Pathol 14:170–175CrossRefGoogle Scholar
  2. 2.
    Sun J, Huang SH, Zhu YC, Whiteman M, Wang MJ, Tan BK, Zhu YZ (2005) Anti-oxidative stress effects of Herba leonuri on ischemic rat hearts. Life Sci 76:3043–3056CrossRefGoogle Scholar
  3. 3.
    Kalenikova EI, Gorodetskaya EA, Murashev AN, Ruuge EK, Medvedev OS (2004) Role of reactive oxygen species in the sensitivity of rat hypertrophied myocardium to ischemia. Biochemistry (Mosc) 69(3):311–316CrossRefGoogle Scholar
  4. 4.
    Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D (1993) Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 342:1007–1011CrossRefGoogle Scholar
  5. 5.
    Shon MY, Choi SD, Kahng GG, Nam SH, Sung NJ (2004) Antimutagenic, antioxidant and free radical scavenging activity of ethyl acetate extracts from white, yellow and red onions. Food Chem Toxicol 42:659–666CrossRefGoogle Scholar
  6. 6.
    Helen A, Krishnakumar K, Vijayammal PL, Augusti KT (2000) Antioxidant effect of onion oil (Allium cepa. Linn) on the damages induced by nicotine in rats as compared to aipha-tocopherol. Toxicol Lett 116:61–68CrossRefGoogle Scholar
  7. 7.
    Lancaster JE, Kelly KE (1983) Quantitative analysis of the S-alk(en)yl-l-cysteine sulphoxides in onion (Allium cepa L.). J Sci Food Agr 34:1229–1235CrossRefGoogle Scholar
  8. 8.
    Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22:659–661CrossRefGoogle Scholar
  9. 9.
    Center for Drug Evaluation and Research (2005) Pharmacology and toxicology, guidance for industry. Estimating the maximum safe dose in initial clinical trials for therapeutics in adult healthy volunteers, p 7. Available at
  10. 10.
    Kim MJ, Moon CH, Kim MY, Lee S, Yi KY, Yoo SE, Lee SH, Baik EJ, Jung YS (2005) KR-32570, a novel Na+/H+ exchanger-1 inhibitor, attenuates hypoxia-induced cell death through inhibition of intracellular Ca2+ overload and mitochondrial death pathway in H9c2 cells. Eur J Pharmacol 525:1–7CrossRefGoogle Scholar
  11. 11.
    Kim MY, Kim MJ, Yoon IS, Ahn JH, Lee SH, Baik EJ, Moon CH, Jung YS (2006) Diazoxide acts more as a PKC-ε activator, and indirectly activates the mitochondrial KATP channel conferring cardioprotection against hypoxic injury. Br J Pharmacol 149:1059–1070CrossRefGoogle Scholar
  12. 12.
    Cuendet M, Potterat O, Salvi A, Testa B, Hostettmann K (2000) A stilbene and dihydrochalcones with radical scavenging activities from Loiseleuria procumbens. Phytochemistry 54:871–874CrossRefGoogle Scholar
  13. 13.
    Krijnen PA, Nijmeijer R, Meijer CJ, Visser CA, Hack CE, Niessen HW (2002) Apoptosis in myocardial ischaemia and infarction. J Clin Pathol 55:801–811CrossRefGoogle Scholar
  14. 14.
    Dumay A, Rincheval V, Trotot P, Mignotte B, Vayssiere JL (2006) The superoxide dismutase inhibitor diethyldithiocarbamate has antagonistic effects on apoptosis by triggering both cytochrome c release and caspase inhibition. Free Radic Biol Med 40:1377–1390CrossRefGoogle Scholar
  15. 15.
    MacLellan WR, Schneider MD (1997) Death by design. Programmed cell death in cardiovascular biology and disease. Circ Res 81:137–144Google Scholar
  16. 16.
    McCord JM, Roy RS, Schaffer SW (1985) Free radicals and myocardial ischemia. The role of xanthine oxidase. Adv Myocardiol 5:183–189Google Scholar
  17. 17.
    Thompson-Gorman SL, Zweier JL (1990) Evaluation of the role of xanthine oxidase in myocardial reperfusion injury. J Biol Chem 265:6656–6663Google Scholar
  18. 18.
    Kinugasa Y, Ogino K, Furuse Y, Shiomi T, Tsutsui H, Yamamoto T, Igawa O, Hisatome I, Shigemasa C (2003) Allopurinol improves cardiac dysfunction after ischemia-reperfusion via reduction of oxidative stress in isolated perfused rat hearts. Circ J 67:781–787CrossRefGoogle Scholar
  19. 19.
    Kendler BS (1987) Garlic (Allium sativum) and onion (Allium cepa): a review of their relationship to cardiovascular disease. Prev Med 16:670–685CrossRefGoogle Scholar
  20. 20.
    Banerjee SK, Dinda AK, Manchanda SC, Maulik SK (2002) Chronic garlic administration protects rat heart against oxidative stress induced by ischemic reperfusion injury. BMC Pharmacol 2:16CrossRefGoogle Scholar
  21. 21.
    Vardar-Unlü G, Candan F, Sökmen A, Daferera D, Polissiou M, Sökmen M, Dönmez E, Tepe B (2003) Antimicrobial and antioxidant activity of the essential oil and methanol extracts of Thymus pectinatus Fisch. et Mey. Var. pectinatus (Lamiaceae). J Agric Food Chem 51:63–67CrossRefGoogle Scholar
  22. 22.
    Aoyama S, Yamamoto Y (2007) Antioxidant activity and flavonoid content of Welsh onion (Allium fistulosum) and the effect of thermal treatment. Food Sci Technol Res 13:67–72CrossRefGoogle Scholar
  23. 23.
    Griffiths G, Trueman L, Crowther T, Thomas B, Smith B (2002) Onions—a global benefit to health. Phytother Res 16:603–615CrossRefGoogle Scholar
  24. 24.
    Shahidi F, Janitha PK, Wanasundara PK (1992) Phenolic antioxidants. Crit Rev Food Sci Nutr 32:67–103CrossRefGoogle Scholar
  25. 25.
    Klanns-Dieter A (1983) Sulfur contends free radicals. In: Nygaard OF, Simic MG (eds) Radioprotectors and anticarcinogens. Academic Press, New York, pp 23–42Google Scholar
  26. 26.
    Myhrstad MC, Carlsen H, Nordström O, Blomhoff R, Moskaug JØ (2002) Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter. Free Radic Biol Med 32:386–393CrossRefGoogle Scholar
  27. 27.
    Akao M, O’Rourke B, Teshima Y, Seharaseyon J, Marbán E (2003) Mechanistically distinct steps in the mitochondrial death pathway triggered by oxidative stress in cardiac myocytes. Circ Res 92:186–194CrossRefGoogle Scholar
  28. 28.
    Borutaite V, Brown GC (2003) Mitochondria in apoptosis of ischemic heart. FEBS Lett 541:1–5CrossRefGoogle Scholar
  29. 29.
    Dzeja PP, Pucar D, Redfield MM, Burnett JC, Terzic A (1999) Reduced activity of enzymes coupling ATP-generating with ATP-consuming processes in the failing myocardium. Mol Cell Biochem 201:33–40CrossRefGoogle Scholar
  30. 30.
    El-Shemy HA, Aboul-Enein AM, Aboul-Enein KM, Fujita K (2007) Willow leaves’ extracts contain anti-tumor agents effective against three cell types. PLoS ONE 2(1):e178CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sok Park
    • 1
  • Mi-Young Kim
    • 1
    • 2
  • Dong Ha Lee
    • 1
    • 2
  • Soo Hwan Lee
    • 1
  • Eun Joo Baik
    • 1
  • Chang-Hyun Moon
    • 1
  • Se Won Park
    • 3
  • Eun Young Ko
    • 3
  • Sei-Ryang Oh
    • 4
  • Yi-Sook Jung
    • 1
    • 2
    Email author
  1. 1.Department of Physiology, School of MedicineAjou UniversitySuwonSouth Korea
  2. 2.Department of Molecular Science and TechnologyAjou UniversitySuwonSouth Korea
  3. 3.College of Life and Environmental SciencesKonkuk UniversitySeoulSouth Korea
  4. 4.Natural Medicine Research CenterKRIBBDaejeonSouth Korea

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