, Volume 47, Issue 3, pp 218–224 | Cite as

Effects of an Extract of Salvia Miltiorrhiza on a Penicillin-Induced Epilepsy Model in Rats

  • A. Bahadir
  • S. Demir
  • H. Orallar
  • E. Beyazcicek
  • F. Oner

In a penciling-induced epilepsy model, Wistar rats (16 males, 16 females) were i.p. administered with an extract of Salvia miltiorrhiza (SmE; total dose 50 mg/kg) once a day for 15 days. The rats were divided into four equal groups, control and SmE-treated for each sex. After the treatment period, an epilepsy model was produced by penicillin G injection (500 IU) into the motor cortex; the electrocorticogram (EcoG) was recorded for 120 min, and statistical analysis was performed. In the male control group with penicillin-induced epilepsy, the spike frequency was significantly (P < 0.05) higher than that in the female control group. The frequency values have been significantly (P < 0.01) increased within the observation period in the female SmE-treated group, while the respective values significantly (P < 0.05) decreased in the analogous male group. There were insignificant differences in the amplitude values and latency to onset of the spike/wave events between female/male SmE and female/male control groups (P > 0.05). Thus, the SmE exerts anticonvulsant effects in the male rat group, while its effect should be characterized as proconvulsant in the female group in the penicillin-induced epilepsy model. The difference (related to the presence of estrogen analogs in the SmE) is determined by dissimilar hormonal backgrounds in males and females. The SmE may be considered as the base for development of anticonvulsant drugs for clinical therapy of epilepsy in the future.


Salvia miltiorrhiza electrocorticography penicillin-induced epileptiform activity rats 


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  1. 1.
    J. W. Sander and S. D. Shorvon, “Incidence and prevalence studies in epilepsy and their methodological problems: a review,” J. Neurol. Neurosurg. Psychiat., 50, No. 7, 829–839 (1987).PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    A. K. Ngugi, S. M. Kariuki, C. Bottomley, et al., “Incidence of epilepsy. A systemic review and meta analysis,” Neurology, 77, No. 10, 1005–1012 (2011).PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    D. M. Treiman, “GABAergic mechanisms in epilepsy,” Epilepsia, 42, Suppl. 3, 8–12 (2001).Google Scholar
  4. 4.
    M. Tan and U. Tan, “Sex difference in susceptibility to epileptic seizures in rats: importance of estrous cycle,” Int. J. Neurosci., 108, Nos. 3/4, 175–191 (2001).CrossRefPubMedGoogle Scholar
  5. 5.
    A. E. Medina, A. C. Manhães, and S. L. Schmidt, “Sex differences in sensitivity to seizures elicited by pentylenetetrazol in mice,” Pharmacol. Biochem. Behav., 68, No. 3, 591–596 (2001).CrossRefPubMedGoogle Scholar
  6. 6.
    M. Tan, N. I. Kalyoncu, and U. Tan, “Sex difference in susceptibility to picrotoxin-induced seizures in rats following octreotide,” Int. J. Neurosci., 112, No. 8, 903-911(2002).CrossRefPubMedGoogle Scholar
  7. 7.
    S. Peternal, K. Pilipovic, and G. Zupan, “Seizure susceptibility and the brain regional sensitivity to oxidative stress in male and female rats in the lithiumpilocarpine model of temporal lobe epilepsy,” Prog. Neuropsychopharmacol. Biol. Psychiat., 33, No. 3, 456–462 (2009).CrossRefGoogle Scholar
  8. 8.
    R. S. Fisher, “Animal model of the epilepsies,” Brain Res. Rev., 14, No. 3, 245–278 (1989).CrossRefPubMedGoogle Scholar
  9. 9.
    D. Contrera, “Experimental models in epilepsy,” Rev. Neurol., 30, No. 4, 370–376 (2000).Google Scholar
  10. 10.
    M. Ayyildiz, M. Yildirim, E. Agar, and A. K. Baltaci, “The effects of leptin on penicillin induced epileptiform activity in the rats,” Brain Res. Bull., 68, No. 5, 374–378 (2006).CrossRefPubMedGoogle Scholar
  11. 11.
    F. M. Gokce, F. Bagirici, S. Demir, et al., “The effect of neuronal nitric oxide synthase inhibitor 7- nitroindazole on the cell death induced by zinc administration in the brain of rats,” Turk. J. Med. Sci., 39, No. 2, 197–202 (2009).Google Scholar
  12. 12.
    M. E. Garcia Garcia, I. Garcia Morales, and J. Matías Guiu, “Experimental models in epilepsy,” Neurologia, 25, No. 3, 181–188 (2010).CrossRefPubMedGoogle Scholar
  13. 13.
    M. Yildirim, M. Ayyildiz, and E. Agar, “Endothelial nitric oxide synthase activity is involved in the protective effect of ascorbic acid against penicillininduced epileptiform activity,” Seizure, 19, No. 2, 102–108 (2010).CrossRefPubMedGoogle Scholar
  14. 14.
    G. Wake, J. Court, A. Pickering, et al., “CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory,” J. Ethnopharmacol., 69, No. 2, 105–114 (2000).CrossRefPubMedGoogle Scholar
  15. 15.
    S. Savelev, E. Okello, N. S. L. Perry, et al., “Synergistic and antogonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil,” Biochem. Pharmacal. Behav., 75, No. 3, 661–668 (2003).CrossRefGoogle Scholar
  16. 16.
    S. E. Kintsizos, Sage. The Genus Salvia, Harward Acad. Publ., Taylor & Francis e-Library (2005), pp. 206–216.Google Scholar
  17. 17.
    D. Baricevic and T. Bartol, “The biological/pharmacological activity of the Salvia genus,” in: SAGE––The Genus Salvia, S. E. Kintzios (ed.), Harvard Acad. Publ., Amsterdam (2000), pp. 143–184.Google Scholar
  18. 18.
    M. E. Cuvelier, C. Berset, and H. Richard, “Antioxidant constituents in sage (Salvia officinalis),” J. Agric. Food Chem., 42, No. 3, 665–669 (1994).CrossRefGoogle Scholar
  19. 19.
    M. Wang, J. Li, M. Rangarajan, et al., “Antioxidative phenolic compounds from sage (Salvia offcinalis),” J. Agric. Food Chem., 46, No. 12, 4869–4873 (1998).CrossRefGoogle Scholar
  20. 20.
    J. Hohmann, I. Zupko, D. Redei, et al., “Protective effects of the aerial parts of Salvia officinalis, Melissa officinalis and Lavandula angustifolia and their constituents against enzyme-dependent and enzymeindependent lipid peroxidation,” Planta Med., 65, No. 6, 576–578 (1999).CrossRefPubMedGoogle Scholar
  21. 21.
    Y. R. Lu and L.Y Foo, “Salvianolic acid, a potent phenolic antioxidant from Salvia officinalis,” Tetrahedron Lett., 42, No. 46, 8223–8225 (2001).CrossRefGoogle Scholar
  22. 22.
    I. Zupko, J. Hohmann, D. Redei, et al., “Antioxidant activity of leaves of Salvia species in enzyme dependent and enzyme-independent systems of lipid peroxidation and their phenolic constituents,” Planta Med., 67, No. 4, 366–368 (2001).CrossRefPubMedGoogle Scholar
  23. 23.
    A. Sivropoulou, C. Nikolaou, E. Papanikolaou, et al., “Antimicrobial, cytotoxic and antiviral activities of Salvia fructicosa essential oil,” J. Agric. Food. Chem., 45, No. 8, 3197–3201 (2006).CrossRefGoogle Scholar
  24. 24.
    P. N. Chang, J. C. Mao, S. H. Huang, et al., “Analysis of cardioprotective effects using purified Salvia miltiorrhiza extract on isolated rat hearts,” J. Pharmacol. Sci., 101, No. 3, 245–249 (2006).CrossRefPubMedGoogle Scholar
  25. 25.
    J. Velíšková, “Estrogens and epilepsy: why are we so excited,” Neuroscientist, 13, No. 1, 77–88 (2007).CrossRefPubMedGoogle Scholar
  26. 26.
    J. Velíšková and K. A. DeSantis, “Sex and hormonal influences on seizures and epilepsy,” Horm. Behav., 63, No. 2, 267–277 (2013).PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    M. Eidi, A. Eidi, and M. Bahar, “Effects of Salvia officinalis L. (sage) leaves on memory retention and its interaction with the cholinergic system in rats,” Nutrition, 22, No. 3, 321–326 (2006).CrossRefPubMedGoogle Scholar
  28. 28.
    R. W. Olsen, “The GABA postsynaptic membrane receptor – ionophore complex. Site of action of convulsant and anticonvulsant drugs,” Mol. Cell Biochem., 39, No. 2, 261–279 (1981).CrossRefPubMedGoogle Scholar
  29. 29.
    D. Pericic, H. Manev, and J. Geber, “Sex related differences in the response of mice, rats and cats to administration of picrotoxin,” Life Sci., 38, No. 10, 905–913 (1986).CrossRefPubMedGoogle Scholar
  30. 30.
    R. L. Macdonald and R. W. Olsen, “GABA receptor channels,” Annu. Rev. Neurosci., 17, No. 1, 569–602 (1994).CrossRefPubMedGoogle Scholar
  31. 31.
    T. Backstrom, K. W. Gee, N. Lan, et al., “Steroids in relation to epilepsy and anaesthesia,” in: Steroids and Neuronal Activity. CIBA Foundation Symposium, D. Chadwick and K. Widdows (eds.), vol. 153. London, Wiley (1990), pp. 225–229.Google Scholar
  32. 32.
    J. Christensen, M. J. Kjeldsen, H. Andersen, et al., “Gender differences in epilepsy,” Epilepsia, 46, No. 6, 956–960 (2005).CrossRefPubMedGoogle Scholar
  33. 33.
    F. Nicoletti, C. Speciale, M. A. Sortino, et al., “Comparative effects of estradiol benzoate, the antiestrogen clomiphene citrate, and the progestin medroxyprogesterone acetate on kainic acid-induced seizures in male and female rats,” Epilepsia, 26, No. 3, 252–257 (1985).CrossRefPubMedGoogle Scholar
  34. 34.
    C. A. Mejias Aponte, C. A. Jimenez Rivera, and A. C. Segarra, “Sex differences in models of temporal lobe epilepsy: role of testosterone,” Brain Res., 944, Nos. 1/2, 210–218 (2002).CrossRefPubMedGoogle Scholar
  35. 35.
    H. E. Scharfman, G. H. Malthankar Phatak, D. Friedman, et al., “A rat model of epilepsy in women: a tool to study physiological interactions between endocrine systems and seizures,” Endocrinology, 150, No. 9, 4437–4442 (2009).PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    C. L. Harden, B. G. Nikolov, P. Kandula, et al., “Effect of levetiracetam on testosterone levels in male patients,” Epilepsia, 51, No. 11, 2348–2351 (2010).CrossRefPubMedGoogle Scholar
  37. 37.
    M. J. Morrell, “Hormones and epilepsy through the lifetime,” Epilepsia, 33, No. Suppl. 4, S49-S61 (1992).CrossRefPubMedGoogle Scholar
  38. 38.
    H. E. Scharfman and N. J. Mac Lusky, “The influence of gonadal hormones on neuronal excitability, seizures, and epilepsy in the female,” Epilepsia, 47, No. 9, 1423–1440 (2006).PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    C. S. Woolley, “Effects of estrogen in the CNS,” Current Opin. Neurobiol., 9, No. 3, 349–354 (1999).CrossRefGoogle Scholar
  40. 40.
    D. S. Reddy and M. A. Rogawski, “Neurosteroid replacement therapy for catamenial epilepsy,” Neurotherapeutics, 6, No. 2, 392–401 (2009).PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of BiophysicsDuzce University Medical SchoolDuzceTurkey
  2. 2.Department of PhysiologyDuzce University Medical SchoolDuzceTurkey
  3. 3.Department of Biology, Faculty of Science and ArtsAbant Izzet Baysal UniversityBoluTurkey

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