title: Ameliorative potential of Colebrookea oppositifolia methanolic root extract against experimental models of epilepsy: Possible role of GABA mediated mechanism.
abstract: BACKGROUND
  Colebrookea oppositifolia Smith is one of the commonly used plants to treat epilepsy by various folk medicine communities like nomadic Gujjars, Tharu and Bhoxa in sub-Himalayan regions of India.
  
  
  OBJECTIVE
  The present study was undertaken to evaluate the anticonvulsant activity of roots of Colebrookea oppositifolia using various experimental models of epilepsy in mice.
  
  
  METHODS
  Petroleum ether extract of roots of C. Oppositifolia (PeCO), methanolic eCO (MeCO) and aqueous eCO (AeCO) was initially evaluated in six-hertz-seizure test in mice, the effective extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) models in mice. In addition, the potent extract was evaluated against the PTZ model by co-administering with flumazenil (FMZ), and also evaluated for its effect on brain GABA levels in brain and NMDA-induced lethality in mice. Furthermore, the possible locomotor deficit-inducing property of the extract was evaluated by actophotometer test in mice.
  
  
  RESULTS
  In six-hertz-seizure test the MeCO (25, 50, 100 and 200mg/kg) and AeCO (50, 100, 200, 400 and 800mg/kg) showed significant protection compared to control group, and MeCO was more potent than AeCO. Based on these outcomes, only MeCO was evaluated in MES and PTZ models. Notably, the MeCO (25, 50, 100 and 200mg/kg) has offered significant and dose- dependent protection against MES and PTZ-induced seizures in mice. Alongside, the MeCO (100 and 200mg/kg) showed a significant increase in GABA levels in the brain compared to control. In line with these findings, the anti-PTZ effect of MeCO (100mg/kg, p.o.) was blocked when co-administered with flumazenil (3mg/kg, i.p.),and in NMDA-induced mortality test, the MeCO has shown only 50% protection at 200mg/kg dose, thus confirmed the significant role of GABA pathway. Interestingly, the MeCO did not cause significant change in locomotor activity compared to before treatment.
  
  
  CONCLUSIONS
  These findings suggest that MeCO possess significant anticonvulsant activity and the outcomes further confirmed the involvement of GABAergic mechanisms behind the anticonvulsant activity of MeCO.
authors.affiliation: Radiant Research Services Pvt. Ltd., Peenya Industrial Area, Bangalore 560058, India. Electronic address: glv_000@yahoo.com.
authors.forename: Gollapalle Lakshminarayanashastry
authors.initials: GL
authors.lastname: Viswanatha
authors.affiliation: Connexios Life Sciences Pvt. Ltd., Basavanagudi, Bangalore 560 004, India.
authors.forename: Marikunte V
authors.initials: MV
authors.lastname: Venkataranganna
authors.affiliation: Oil Technological and Pharmaceutical Research Institute (OTPRI), JNT University Anantapur, Ananthapuramu 515 002, India.
authors.forename: Nunna Bheema Lingeswara
authors.initials: NBL
authors.lastname: Prasad
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004597:Electroshock / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy*; D019686:Lamiaceae / Q000737:chemistry*; D008519:Medicine, Traditional / Q000379:methods; D000432:Methanol / Q000737:chemistry; D051379:Mice; D008962:Models, Theoretical; D010433:Pentylenetetrazole / Q000494:pharmacology; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D010936:Plant Extracts; D012997:Solvents; D005680:gamma-Aminobutyric Acid; D010433:Pentylenetetrazole; D000432:Methanol
keywords: Anticonvulsant; Epilepsy; MES-induced seizures; PTZ-induced seizures; Six-hertz seizures