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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price includes VAT (USA)
Tax calculation will be finalised during checkout.
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).
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).
D. M. Treiman, “GABAergic mechanisms in epilepsy,” Epilepsia, 42, Suppl. 3, 8–12 (2001).
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).
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).
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).
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).
R. S. Fisher, “Animal model of the epilepsies,” Brain Res. Rev., 14, No. 3, 245–278 (1989).
D. Contrera, “Experimental models in epilepsy,” Rev. Neurol., 30, No. 4, 370–376 (2000).
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).
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).
M. E. Garcia Garcia, I. Garcia Morales, and J. Matías Guiu, “Experimental models in epilepsy,” Neurologia, 25, No. 3, 181–188 (2010).
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).
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).
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).
S. E. Kintsizos, Sage. The Genus Salvia, Harward Acad. Publ., Taylor & Francis e-Library (2005), pp. 206–216.
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.
M. E. Cuvelier, C. Berset, and H. Richard, “Antioxidant constituents in sage (Salvia officinalis),” J. Agric. Food Chem., 42, No. 3, 665–669 (1994).
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).
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).
Y. R. Lu and L.Y Foo, “Salvianolic acid, a potent phenolic antioxidant from Salvia officinalis,” Tetrahedron Lett., 42, No. 46, 8223–8225 (2001).
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).
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).
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).
J. Velíšková, “Estrogens and epilepsy: why are we so excited,” Neuroscientist, 13, No. 1, 77–88 (2007).
J. Velíšková and K. A. DeSantis, “Sex and hormonal influences on seizures and epilepsy,” Horm. Behav., 63, No. 2, 267–277 (2013).
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).
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).
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).
R. L. Macdonald and R. W. Olsen, “GABA receptor channels,” Annu. Rev. Neurosci., 17, No. 1, 569–602 (1994).
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.
J. Christensen, M. J. Kjeldsen, H. Andersen, et al., “Gender differences in epilepsy,” Epilepsia, 46, No. 6, 956–960 (2005).
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).
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).
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).
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).
M. J. Morrell, “Hormones and epilepsy through the lifetime,” Epilepsia, 33, No. Suppl. 4, S49-S61 (1992).
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).
C. S. Woolley, “Effects of estrogen in the CNS,” Current Opin. Neurobiol., 9, No. 3, 349–354 (1999).
D. S. Reddy and M. A. Rogawski, “Neurosteroid replacement therapy for catamenial epilepsy,” Neurotherapeutics, 6, No. 2, 392–401 (2009).
About this article
Cite this article
Bahadir, A., Demir, S., Orallar, H. et al. Effects of an Extract of Salvia Miltiorrhiza on a Penicillin-Induced Epilepsy Model in Rats. Neurophysiology 47, 218–224 (2015). https://doi.org/10.1007/s11062-015-9524-z
- Salvia miltiorrhiza
- penicillin-induced epileptiform activity