Curcuma Oil: Reduces Early Accumulation of Oxidative Product and is Anti-apoptogenic in Transient Focal Ischemia in Rat Brain

An Erratum to this article is available

Abstract

Turmeric is a source of numerous aromatic compounds isolated from powdered rhizomes of Curcuma longa Linn. The constituents are present as volatile oil, the Curcuma oil (C.oil), semi-solid oleoresins and non-volatile compounds such as curcumin. A rapidly expanding body of data provides evidence of the anti-cancer action of Curcumin, and most importantly in the present context, its neuroprotective activity. Almost nothing is known about such activity of C.oil. We report that C.oil (500 mg Kg−1 i.p.) 15 min before 2 h middle cerebral artery occlusion (MCAo) followed by 24 h reflow in rats significantly diminished infarct volume, improved neurological deficit and counteracted oxidative stress. The percent ischemic lesion volume on diffusion-weighted imaging was significantly attenuated. Mitochondrial membrane potential, reactive oxygen species, peroxynitrite levels, caspase-3 activities leading to delayed neuronal death were significantly inhibited after treatment with C.oil. These results suggest that the neuroprotective activity of C.oil against cerebral ischemia is associated with its antioxidant activities and further; there is attenuation of delayed neuronal death via a caspase-dependent pathway. C.oil appears to be a promising agent not only for the treatment of cerebral stroke, but also for the treatment of other disorders associated with oxidative stress.

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References

  1. 1.

    Ammon HPT, Wahl MA (1991) Pharmacology of curcuma longa. Planta Med 57:1–7

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Jayaprakasha GK, Rao LJM, Sakariah KK (2002a) Improved HPLC method for the determination of curcumin, demethoxycurcumin and bisdemethoxycurcumin. J Agric Food Chem 50:3668–3672

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Jayaprakasha GK, Jena BS, Negi PS et al (2002b) Evaluation of antioxidant activities and antimutagenicity of turmeric oil—a byproduct from curcumin production. Zeitschrift f¨ur Naturforschung 57c:828–835

    Google Scholar 

  4. 4.

    Rao DS, Sekhara NC, Satyanarayana MN et al (1970) Effect of curcumin on serum and liver cholesterol levels in the rat. J Nutr 100:1307–1315

    PubMed  CAS  Google Scholar 

  5. 5.

    Nirmala C, Puvanakrishnan R (1996) Protective role of curcumin against isoproterenol induced myocardial infarction in rats. Mol Cell Biochem 159:85–93

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Shoskes DA (1998) Effect of bioflavonoids quercetin and curcumin on ischemic renal injury: a new class of renoprotective agents. Transplantation 66(2):147–152

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Rajakrishnan V, Viswanathan P, Rajasekharan KN et al (1999) Neuroprotective role of curcumin from Curcuma longa on ethanol-induced brain damage. Phytother Res 13:571–574

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Ray M, Pal R, Singh S, Khanna NM (2006) Herbal medicament for the treatment of neurocerebrovascular disorders. US patent number 6991814, grant date: 31-jan2006

  9. 9.

    Jain V, Prasad V, Pal R, Singh S (2007) Standardization and stability studies of neuroprotective lipid soluble fraction obtained from Curcuma longa. J Pharm Biomed Anal 44:1079–1086

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Gershenzon J, Dudareva N (2007) The function of terpene natural products in the natural world. Nat Chem Biol 3:408–414

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Longa ZE, Weinstein PR, Carlson S et al (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91

    PubMed  CAS  Google Scholar 

  12. 12.

    Rastogi L, Godbole MM, Ray M et al (2006) Reduction in oxidative stress and cell death explains hypothyroidism induced neuroprotection subsequent to ischemia/reperfusion insult. Exp Neurol 200:290–300

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Sinha K, Degaonkar MN, Jagannathan NR et al (2001) Effect of melatonin on ischemia reperfusion injury induced by middle cerebral artery occlusion in rats. Euro J Pharmacol 428:185–192

    Article  CAS  Google Scholar 

  14. 14.

    Bederson JB, Pitts LH, Tsuji M et al (1986). Rat middle cerebral artery occlusion: evaluation of the model and development of a neurological examination. Stroke 17:472–476

    PubMed  CAS  Google Scholar 

  15. 15.

    Belayev L, Busto R, Zhao W et al (1995) Hu-211, a novel noncompetitive N-Methyl-d-aspartate antagonist, improves neurological deficit and reduces infarct volume after reversible focal cerebral ischemia in rat. Stroke 26:2313–2320

    PubMed  CAS  Google Scholar 

  16. 16.

    Nishikimi M, Rao NA, Yagi K (1972) The occurrence of superoxide anion in the reaction of reduced PMS and molecular oxygen. Biochem Biophys Res Commun 46:849–854

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Aebi H (1974) Catalase. In: Bergmeyer HU (ed) Methods of Enzymatic Analysis, 3rd edn. Academic Press, New York and London, 2:673–684

  18. 18.

    Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Clin Med 70:158–169

    CAS  Google Scholar 

  19. 19.

    Okhawa H, Ohishi N, Yagi K (1979) Assay of lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  Google Scholar 

  20. 20.

    Lowry OH, Rosebrough NI, Farr AL et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  21. 21.

    Oyama Y, Ueha T, Hayashi A et al (1992) Flowcytometric estimation of the effect of Gingko biloba extract on the content of hydrogen peroxide in dissociated mammalian neurons. Jpn J Pharmacol 60:385–388

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Boldyrev A, Carpenter D, Huentelman M et al (1999) Sources of ROS production in exotoxin-stimulated cerebellar granule cells. Biochem Biophys Res Commun 256:320–324

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Dringen R (2000) Metabolism and functions of glutathione in brain. Prog Neurobiol 62:649–671

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Kong LD, Zhang Y, Pan X et al (2000) Inhibition of xanthine oxidase by liquiritigenin and isoliquiritigenin isolated from Sinofranchetia chinensis. Cell Mol Life Sci 57:500–505

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Shah ZA, Gilani RA, Sharma P et al (2005) Cerebroprotective effect of Korean ginseng tea against global and focal models of ischemia in rats. J Ethno pharmacol 101:299–307

    CAS  Google Scholar 

  26. 26.

    Thomas CE, Mclean LR, Parker PA et al (1992) Ascorbate and phenolic antioxidant interactions in prevention of liposomal oxidation. Lipids 27:543–550

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Kaneko T, Kaii K, Matsua M (1994) Protection of linoleic acid hydroperoxide-induced cytotoxicity by phenolic antioxidants. Free radic Biol Med 16:969–985

    Article  Google Scholar 

  28. 28.

    Turgut T, Richard AD, Carano MS et al (1998) A novel endothelin antagonist, A-127722, attenuates ischemic lesion size in rats with temporary middle cerebral artery occlusion. Stroke 29:850–858

    Google Scholar 

  29. 29.

    Lo EH, Pierce AR, Mandeville JB et al (1997). Neuroprotection with NBQX in rats focal cerebral ischemia: effects on ADC probability distribution functions and diffusion perfusion relationship. Stroke 28:439–447

    PubMed  CAS  Google Scholar 

  30. 30.

    Li F, Liu K, Silva MD et al (2000). Transient and permanent resolution of ischemic lesions on diffusion weighted imaging after brief periods of focal ischemia in rats. Stroke 31:946–954

    PubMed  CAS  Google Scholar 

  31. 31.

    Minematsu K, Li L, Sotak CH et al (1992). Reversible focal ischemic injury demonstrated by diffusion weighted magnetic resonance imaging in rats. Stroke 23:1304–1311

    PubMed  CAS  Google Scholar 

  32. 32.

    Tatlisumak T, Carano RAD, Takano K et al (1998). A novel endothelium antagonist, A-127722, attenuates ischemic lesion size in rats with temporary middle cerebral artery occlusion a diffusion and perfusion MRI study. Stroke 29:850–857

    PubMed  CAS  Google Scholar 

  33. 33.

    Votyakova TV, Reynolds YN (2001) Delta Psi (m)-dependent production of reactive oxygen species by rat brain mitochondria. J Neurochem 79:266–277

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Dykens JA (1994) Isolated cerebral and cerebellar mitochondria produce free radicals when exposed to elevated Ca 2+and Na +: implications for neurodegeneration. J Neurochem 63:584–591

    PubMed  CAS  Article  Google Scholar 

  35. 35.

    Cao W, Carney JM, Duchen A et al (1988) Oxygen free radical involvement in ischaemia and reperfusion injury to brain. Neurosci Lett 88:233–238

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Chan PH (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21:2–14

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Joshi J, Ghaisas S, Vaidya A et al (2003) Early human safety study of turmeric oil (Curcuma longa oil) administered orally in healthy volunteers. J Assoc Physicians India 51:1055–1060

    PubMed  Google Scholar 

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Acknowledgments

Priyanka Rathore and Preeti Dohare thank CSIR for providing fellowships.

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Correspondence to Madhur Ray.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s11064-008-9787-5

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Rathore, P., Dohare, P., Varma, S. et al. Curcuma Oil: Reduces Early Accumulation of Oxidative Product and is Anti-apoptogenic in Transient Focal Ischemia in Rat Brain. Neurochem Res 33, 1672–1682 (2008). https://doi.org/10.1007/s11064-007-9515-6

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Keywords

  • Curcuma oil
  • MCAo
  • Rat
  • Ischemia
  • Reperfusion
  • Antioxidants
  • SOD
  • CAT
  • GSH-Px
  • Caspase-3
  • ROS
  • Mitochondrial membrane potential
  • Peroxynitrite
  • Apoptosis
  • Necrosis