Cerebroprotective activity of Wedelia calendulacea on global cerebral ischemia in rats


The present study was to investigate the effect of W. calendulacea on ischemia and reperfusion-induced cerebral injury. Cerebral ischemia was induced by occluding right and left common carotid arteries (global cerebral ischemia) for 30 min followed by reperfusion for 1 h and 4 h individually. Various biochemical alterations, produced subsequent to the application of bilateral carotid artery occlusion (BCAO) followed by reperfusion viz. increase in lipid peroxidation (LPO), hydrogen peroxide (H2O2), and decrease in reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD), level in the brain tissue, Western blot analysis (Cu-Zn-SOD and CAT) and assessment of cerebral infarct size were measured. All those enzymes are markedly reversed and restored to near normal level in the groups pretreated with W. calendulacea (250 and 500 mg/kg given orally in single and double dose/day for 10 days) in dose-dependent way. The effect of W. calendulacea had increased significantly the protein expression of copper/zinc superoxide dismutase (Cu-Zn-SOD) and CAT in cerebral ischemia. W. claendulacea was markedly decrease cerebral infarct damages but results are not statistically significant. It can be concluded that W. calendulacea possesses a neuroprotective activity against cerebral ischemia in rat.


  1. 1.

    Bederson, J. B., Pitts, L. H., Germano, S. M., Nishimura, M. C., Davis, R. L., Bartkowski, H. M. (1986) Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke 17, 1304–1308.

    CAS  Article  Google Scholar 

  2. 2.

    Chan, P. H. (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J. Cereb. Blood Metab. 21, 2–14.

    CAS  Article  Google Scholar 

  3. 3.

    Claiborne, A. (1985) Catalase activity, In: Greenwald, R. A. (ed.), Hand Book of Methods for Oxygen Radical Research. CRC Press, Boca Raton, Florida, USA, pp. 283–284.

    Google Scholar 

  4. 4.

    Cui, Ke., Luo, X., Xu, K., Murthy, M. R. V. (2004) Role of oxidative stress in neurodegeneration: recent developments in assay methods for oxidative stress and nutraceutical antioxidants. Prog. Neuropsychopharmacol. Biol. Psychiatry 28, 771–799.

    CAS  Article  Google Scholar 

  5. 5.

    Cuzzocrea, S., McDonald, M. C., Mazzon, E., Siriwardena, D., Costantino, G., Fulia, F., Cucinotta, G., Gitto, E., Cordaro, S., Barberi, I., De Sarro, A., Caputi, A. P., Thiemermann, C. (2000) Effects of tempol, a membrane-permeable radical scavenger, in a gerbil model of brain injury. Brain Res. 875, 96–106.

    CAS  Article  Google Scholar 

  6. 6.

    Dhindsa, R. S., Plumb-Dhindsa, P., Thorpe, T. A. (1981) Leaf senescence: correlated with increased levels of membrane permeability and lipid peroxidation, and decreased levels of superoxide dismutase and catalase. J. Exp. Botany 32, 93–101.

    CAS  Article  Google Scholar 

  7. 7.

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

    CAS  Article  Google Scholar 

  8. 8.

    Fridovich, I. (1975) Superoxide dismutases. Annu. Rev. Biochem. 44, 147–159.

    CAS  Article  Google Scholar 

  9. 9.

    Gaspar, T., Domoki, F., Lenti, L., Institoris, A., Snipes, J. A., Bari, F., Busija, D. W. (2009) Neuroprotective effect of adenoviral catalase gene transfer in cortical neuronal cultures. Brain Res. 270, 1–9.

    Article  Google Scholar 

  10. 10.

    Gutteridge, J. M. C., Halliwell, B. (1994) Antioxidants in Nutrition, Health and Disease. Oxford University Press.

    Google Scholar 

  11. 11.

    Govindachari, T. R., Premila, M. S. (1985) The benzofuran norwedelic acid from Wedelia calendulacea. Phytochemistry 24, 3068.

    CAS  Article  Google Scholar 

  12. 12.

    Harlow, L., Lane, D. (1988) Antibodies: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.

    Google Scholar 

  13. 13.

    Imaizumi, S., Tominaga, T., Uenohara, H., Yoshimoto, T., Suzuki, J., Fujita, Y. (1986) Initiation and propagation of lipid peroxidation in cerebral infarction models. Experimental studies. Neurol. Res. 8, 214–220.

    CAS  Article  Google Scholar 

  14. 14.

    Imaizumi, S., Kayama, T., Suzuki, J. (1984) Chemiluminescence in hypoxic brain-the first report. Correlation between energy metabolism and free radical reaction. Stroke 15, 1061–1065.

    CAS  Article  Google Scholar 

  15. 15.

    Jollow, D. J., Mitchell, J. R., Zampaghone, N., Gillete, J. R. (1974) Bromobenzene induced oxide as the hepatotoxic intermediate. Pharmacology 11, 161–169.

    Article  Google Scholar 

  16. 16.

    Kelsey, N. A., Wilkins, H. M., Linseman, D. A. (2010) Nutraceutical antioxidants as novel neuroprotective agents. Molecules 15, 7792–7814.

    CAS  Article  Google Scholar 

  17. 17.

    Kim, Y. C. (2010) Neuroprotective phenolics in medicinal plants. Arch. Pharm. Res. 33, 1611–1632.

    CAS  Article  Google Scholar 

  18. 18.

    Kobori, M., Yang, Z., Gong, D., Heissmeyer, V., Zhu, H., Jung, Y.-K., Angelica, M., Gakidis, M., Rao, A., Sekine, T., Ikegami, F., Yuan, C., Yuan, J. (2004) Wedelolactone suppresses LPS-induced caspase- 11 expression by directly inhibiting the IKK Complex. Cell Death Differ. 11, 123–130.

    CAS  Article  Google Scholar 

  19. 19.

    Lapchak, P. A., Araujo, D. M. (2007) Advances in ischemic stroke treatment: neuroprotective and combination therapies. Expert. Opin. Emerg. Drugs 12, 97–112.

    CAS  Article  Google Scholar 

  20. 20.

    Lowry, O. H., Rosebrough, N. J., Fair, A. L., Randall, R. J. (1951) Protein measurement with Folin phenol reagent. J. Biol. Chem. 193, 265–275.

    CAS  Google Scholar 

  21. 21.

    Murakami, K., Kondo, T., Kawase, M., Li, Y., Sato, S., Chen, S. F. (1998) Mitochondrial susceptibility to oxidative stress exacerbates cerebral infarction that follows permanent focal cerebral ischemia in mutant mice with manganese superoxide dismutase deficiency. J. Neurosci. 18, 205–213.

    CAS  Article  Google Scholar 

  22. 22.

    Nadkarni, A. K. (1976) Indian Materia medica. I. India Popular Prakashan Pvt. Ltd., Bombay.

    Google Scholar 

  23. 23.

    Oliver, C. N., Starke-Reed, P. E., Stadtman, E. R., Liu, G. J., Carney, J. M., Floyd, R. A. (1990) Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc. Natl. Acad. Sci. U. S. A. 87, 5144–5147.

    CAS  Article  Google Scholar 

  24. 24.

    Prakash, T., Rama Rao, N., Viswanatha Swamy, A. H. M. (2008) Neuropharmacological studies on Wedelia calendulacea Less stem extract. Phytomedicine 15, 959–970.

    CAS  Article  Google Scholar 

  25. 25.

    Ravindranath, V., Reed, D. J. (1990) Glutathione depletion and formation of glutathione-protein mixed disulphide following exposure of brain mitochondria to oxidative stress. Biochem. Biophys. Res. Commun. 169, 1075–1079.

    CAS  Article  Google Scholar 

  26. 26.

    Sakamoto, A., Ohnishi, S. T., Ohnishi, T., Ogawa, R. (1991) Relationship between free radical production and lipid peroxidation during ischemia-reperfusion injury in the rat brain. Brain Res. 554, 186–192.

    CAS  Article  Google Scholar 

  27. 27.

    Schulz, J. B., Lindenau, J., Seyfried, J., Dichgans, J. (2000) Glutathione, oxidative stress and neurodegeneration. Eur. J. Biochem. 267, 4904–4911.

    CAS  Article  Google Scholar 

  28. 28.

    Sims, N. R., Anderson, M. F., Hobbs, L. M., Kong, J. Y., Phillips, S., Powell, J. A., Zaidan, E. (2000) Impairment of brain mitochondrial function by hydrogen peroxide. Mol. Brain Res. 77, 176–184.

    CAS  Article  Google Scholar 

  29. 29.

    Utley, H. C., Bernhein, F., Hochslein, P. (1967) Effects of sulfhydryl reagent on peroxidation in microsomes. Arch. Biochem. Biophys. 260, 521–531.

    Google Scholar 

  30. 30.

    Velikova, V., Yordanov, I., Edreva, A. (2000) Oxidative stress and some antioxidant systems in acid rain treated bean plants protective role of exognous polyamines. Plant Sci. 151, 59–66.

    CAS  Article  Google Scholar 

  31. 31.

    Wagner, H., Geyer, B., Kiso, Y., Hikino, H., Rao, G. S. (1986) Coumestans as main active principles of the liver drugs EcliPta alba and Wedelia calendulaceae. Planta Medica 52, 370–374.

    Article  Google Scholar 

  32. 32.

    Zahoor Ahmad Shah, Rabia Afzal Gilani, Pragya Sharma, Shashi Bharat Vohora (2005) Cerebroprotective effect of Korean ginseng tea against global and focal models of ischemia in rats. J. Ethnopharmacol. 101, 299–307.

    Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to T. Prakash.

Rights and permissions

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Cite this article

Prakash, T., Kotresha, D. & Rao, N.R. Cerebroprotective activity of Wedelia calendulacea on global cerebral ischemia in rats. BIOLOGIA FUTURA 62, 361–375 (2011). https://doi.org/10.1556/ABiol.62.2011.4.3

Download citation


  • Wedelia calendulacea
  • Cu-Zn SOD
  • cerebral infarction
  • brain ischemia
  • Western blot analysis