Effect of Elettaria cardamomum essential oil and its main component (1, 8‐cineole) on brain damage caused by cerebral hypoperfusion by suppressing apoptosis and inflammation in rats


Cerebral hypoperfusion

How to Cite

Farivar, M., Hooshmandi, Z., Setorki, M., & Amini, S. (2020). Effect of Elettaria cardamomum essential oil and its main component (1, 8‐cineole) on brain damage caused by cerebral hypoperfusion by suppressing apoptosis and inflammation in rats. Iranian Red Crescent Medical Journal, 22(12). https://doi.org/10.32592/ircmj.2020.22.12.178


Background: Stroke is one of the most common causes of death in industrialized countries and a leading cause of permanent disability in adults worldwide. Elettaria cardamomum is a widely used nutraceuticalis, which is reported to have diverse functions, including positive effects on anxiety-like behavior properties.

Objective: The present study aimed to determine the effect of Elettaria cardamomum essential oil and its major constituent (i.e., 1,8-cineole) on the brain injury induced by cerebral hypoperfusion in rats.

Materials and Methods: Cerebral hypoperfusion was induced in Wistar rats by the occlusion of the bilateral carotid artery for 30 min. Subsequently, Elettaria cardamomum essential oil (25, 50, and 75 mg/kg i.p.) and its major constituent (1,8-cineole) (5, 10, and 20 mg/kg i.p.) was injected to rats for 14 consecutive days. After the final treatment, blood samples were taken, and the brain tissues were separated and used for biochemical analysis by RT-PCR to detect the levels of proinflammatory cytokines.

Results: Administration of Elettaria cardamomum essential oil and 1,8-cineole significantly decreased the malondialdehyde and nitric oxide levels in the blood and brain cortex of the rat. Additionally, Elettaria cardamomum essential oil and 1,8-cineole significantly suppressed the expression level of Caspase 3, IL-1β, TNF-α, and iNOS in the cerebral cortex.

Conclusions: The findings suggest that Elettaria cardamomum essential oil has specific neuroprotective effects that may be useful for the treatment of cerebral hypoperfusion. The pharmacological mechanism of Elettaria cardamomum partly involves the modulation of inflammatory mediators and oxidative stress.



  1. Mestriner RG, Miguel PM, Bagatini PB, Saur L, Boisserand LSB, Baptista PPA, et al. Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats. Behav Brain Res. 2013; 244:82-9. doi: 10.1016/j.bbr.2013.02.001. [PubMed: 23403282].
  2. Matsumoto S, Murozono M, Kanazawa M, Nara T, Ozawa T, Watanabe Y. Edaravone and cyclosporine A as neuroprotective agents for acute ischemic stroke. Acute Med Surg. 2018;5(3):213-21. doi: 10.1002/ams2.343. [PubMed: 29988669].
  3. Siesjö BK, Elmer E, Janelidze S, Keep M, Kristian T, Ouyang YB, et al. Role and mechanisms of secondary mitochondrial failure. Acta Neurochir Suppl. 1999;73:7-13. doi: 10.1007/978-3-7091-6391-7_2. [PubMed: 10494335].
  4. Radak D, Resanovic I, Isenovic ER. Link between oxidative stress and acute brain ischemia. Angiology. 2014;65(8):667-76. doi: 10.1177/0003319713506516. [PubMed: 24132856].
  5. Margaill I, Plotkine M, Lerouet D. Antioxidant strategies in the treatment of stroke. Free Radic Biol and Med. 2005;39(4):429-43. doi: 10.1016/j.freeradbiomed.2005.05.003. [PubMed: 16043015].
  6. Jamal A, Javed K, Aslam M, Jafri MA. Gastroprotective effect of cardamom, Elettaria cardamomum Maton. fruits in rats. J Ethnopharmacol. 2006;103(2):149-53. doi: 10.1016/j.jep.2005.07.016. [PubMed: 16298093].
  7. Masoumi-Ardakani Y, Mandegary A, Esmaeilpour K, Najafipour H, Sharififar F, Pakravanan M, et al. Chemical composition, anticonvulsant activity, and toxicity of essential oil and methanolic extract of Elettaria cardamomum. Planta Med. 2016;82(17):1482-6. doi: 10.1055/s-0042-106971. [PubMed: 27433883].
  8. Mahmud S. Composition of essential oil of Elettaria cardamomum Maton leaves. Pakistan J Sci. 2008;60:111–4.
  9. Santos F, Rao V. Antiinflammatory and antinociceptive effects of 1, 8‐cineole a terpenoid oxide present in many plant essential oils. Phytother Res. 2000;14(4):240-4. doi: 10.1002/1099-1573(200006)14:4<240::aid-ptr573>3.0.co;2-x. [PubMed: 10861965].
  10. Ahmadvand H, Amiri H, Dalvand H, Bagheri S. Various antioxidant properties of essential oil and hydroalcoholic extract of Artemisapersica.J Birjand Univ Med Sci. 2014;20(4):416–24.
  11. Nakashima M, Niwa M, Iwai T, Uematsu T. Involvement of free radicals in cerebral vascular reperfusion injury evaluated in a transient focal cerebral ischemia model of rat. Free Radic Biol Med. 1999;26(5-6):722-9. doi: 10.1016/s0891-5849(98)00257-3. [PubMed: 10218662].
  12. Sadeek EA, El-Razek FH. The chemo-protective effect of turmeric, chili, cloves and cardamom on correcting iron overload-induced liver injury, oxidative stress and serum lipid profile in rat models. J am Sci. 2010;6(10):7.
  13. Singh G, Kiran S, Marimuthu P, Isidorov V, Vinogorova V. Antioxidant and antimicrobial activities of essential oil and various oleoresins of Elettaria cardamomum (seeds and pods). J Sci Food Agricul. 2008;88(2):280-9. doi: 10.1002/jsfa.3087.
  14. Saeed A, Sultana B, Anwar F, Mushtaq M, Alkharfy KM, Gilani A-H. Antioxidant and antimutagenic potential of seeds and pods of green cardamom (Elettaria cardamomum). Int J Pharmacol. 2014;10:461-9.
  15. Ciftci O, Ozdemir I, Tanyildizi S, Yildiz S, Oguzturk H. Antioxidative effects of curcumin, β-myrcene and 1,8-cineole against 2,3,7, 8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in rats liver. Toxicol Ind Health. 2011;27(5):447-53. doi: 10.1177/0748233710388452. [PubMed: 21245202].
  16. Lerouet D, Beray-Berthat V, Palmier B, Plotkine M, Margaill I. Changes in oxidative stress, iNOS activity and neutrophil infiltration in severe transient focal cerebral ischemia in rats. Brain Res. 2002;958(1):166-75. doi: 10.1016/s0006-8993(02)03685-5. [PubMed: 12468042].
  17. Satou T, Takahashi M, Kasuya H, Murakami S, Hayashi S, Sadamoto K, et al. Organ accumulation in mice after inhalation of single or mixed essential oil compounds. Phytother Res. 2013;27(2):306-11. doi: 10.1002/ptr.4723. [PubMed: 22581512].
  18. Ryu S, Park H, Seol GH, Choi IY. 1,8‐C ineole ameliorates oxygen‐glucose deprivation/reoxygenation‐induced ischaemic injury by reducing oxidative stress in rat cortical neuron/glia. J Pharm Pharmacol.2014;66(12):1818-26. doi: 10.1111/jphp.12295.
  19. Juergens UR, Stöber M, Vetter H. Inhibition of cytokine production and arachidonic acid metabolism by eucalyptol (1.8-cineole) in human blood monocytes in vitro. Eur J Med Res. 1998;3:508-10. [PubMed: 9810029].
  20. Linghu K, Lin D, Yang H, Xu Y, Zhang Y, Tao L, et al. Ameliorating effects of 1, 8-cineole on LPS-induced human umbilical vein endothelial cell injury by suppressing NF-κB signaling in vitro. Eur J Pharmacol. 2016;789:195-201. doi: 10.1016/j.ejphar.2016.07.039. [PubMed: 27455900].
  21. Chou ST, Peng HY, Hsu JC, Lin CC, Shih Y. Achillea millefolium L. essential oil inhibits LPS-induced oxidative stress and nitric oxide production in RAW 264.7 macrophages. Int J Mol Sci. 2013;14(7):12978-93. doi: 10.3390/ijms140712978. [PubMed: 23797659].
  22. Chen AQ, Fang Z, Chen XL, Yang S, Zhou YF, Mao L, et al. Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain–barrier disruption after ischemic stroke. Cell Death Dis. 2019;10(7):1-18. doi: 10.1038/s41419-019-1716-9. [PubMed: 31221990].
  23. Lee JH, Park SY, Shin YW, Hong KW, Kim CD, Sung SM, et al. Neuroprotection by cilostazol, a phosphodiesterase type 3 inhibitor, against apoptotic white matter changes in rat after chronic cerebral hypoperfusion. Brain Res. 2006;082(1):182-91. doi: 10.1016/j.brainres.2006.01.088. [PubMed: 16516167].
  24. Mattson MP, Duan W, Pedersen W, Culmsee C. Neurodegenerative disorders and ischemic brain diseases. Apoptosis. 2001;6(1-2):69-81. doi: 10.1023/a:1009676112184. [PubMed: 11321043].
  25. Kowaltowski AJ, Castilho RF, Vercesi AE. Mitochondrial permeability transition and oxidative stress. FEBS lett. 2001;495(1-2):12-5. doi: 10.1016/S0014-5793(01)02316-X.
  26. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997;91(4):479-89. doi: 10.1016/s0092-8674(00)80434-1. [PubMed: 9390557].