Achyranthes aspera Attenuates epilepsy in experimental animals: possible involvement of GABAergic mechanism
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The present study was aimed to examine the possible anticonvulsant property of aerial parts of Achyranthes aspera using various experimental models of epilepsy in mice. Petroleum ether extract of aerial parts of A. aspera (PeAA), methanolic eAA (MeAA) and aqueous eAA (AeAA) was initially evaluated against six-hertz seizure model in mice, based on the outcomes 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 GABA levels in brain and NMDA-induced lethality in mice. Furthermore, the probable locomotor deficit-inducing property of the extract was evaluated by actophotometer test in mice. In results, only MeAA showed protection against six-hertz-induced seizures in mice, based on these outcomes only MeAA was evaluated in MES and PTZ models. Notably, the MeAA (200, 400 and 800 mg/kg) has offered mild and dose dependent protection against MES and PTZ-induced seizures in mice. Alongside, the MeAA (400 mg/kg) showed a significant increase in GABA levels in the brain compared to control, and in line with these findings the anti-PTZ effect of MeAA (400 mg/kg, p.o.) was blocked when co-administered with flumazenil (5 mg/kg, i.p.). However, the MeAA has not shown significant protection against NMDA-induced mortality and also did not cause significant change in locomotor activity compared to before treatment. These findings suggest that MeAA possess mild anticonvulsant activity and the outcomes further confirmed the involvement of GABAergic mechanism behind the anticonvulsant activity of MeAA.
KeywordsAchyranthes aspera Anticonvulsant Epilepsy Herbal medicine Six-hertz seizures MES –induced seizures PTZ-induced seizures Gamma-amino butyric acid Diazepam
Petroleum ether extract of Achyranthes aspera aerial parts
Methanolic extract of Achyranthes aspera aerial parts
Aqueous extract of Achyranthes aspera aerial parts
Hind limb Tonic extensor
Hind limb Tonic flexion
Gamma amino butyric acid
The authors acknowledge the technical help provided by Dr. Nandakumar K, Associate Professor, Department of Pharmacology, Manipal college of Pharmaceutical sciences, Manipal.
The authors greatly acknowledge Ms.Radiant Research Services Pvt. Ltd., Bangalore, Vitthartha Life Sciences, Bommasandra Industrial Area, Bangalore, and Manipal College of Pharmaceutical Sciences, Manipal for providing all the neccesary facilities and Technical help in completing the research work.
GLV, MVV, NBLP and AG have contributed equally for designing, conducting the study, data collection, analysis and preparation of manuscript, MVV and NBLP involved in critical analysis and interpretation of findings, MVV, NBLP, AG have proof read and approved the final version of manuscript.
Compliance with ethical standards
Conflicts of interest
The authors declare there are no conflicts of interest and they guarantee no further ethical conflict among the authors and the experimental methodology. Also, no formal funding from any agencies was used for this project.
- Barua CC, Talukdar A, Begum SA, Buragohain B, Roy JD, Borah RS, Lahkar M (2009a) Antidepressant-like effects of the methanolic extract of Achyranthes aspera Linn. In Animal Models of Depression Pharmacologyonline 2:587–594Google Scholar
- Barua CC, Roy JD, Buragohain B (2009b) Anxiolytic effects of hydroethanolic extract of Drymariacordata L wild. Ind J Exp Biol 47:969–973Google Scholar
- Carter SO, Banerjee PK, McIntyre B, David H (2000) Modulation of absence seizures by the GABAA receptor: a critical role for metabotropic glutamate receptor 4 (mGluR4). J Neurosci 20:6218–6224Google Scholar
- Chakraborty A, Amudha P, Geetha M (2010) Evaluation of anxiolytic activity of methanolic extract of Sapindusmukorossigaertn in mice. Int J Pharma Bio Sci 1(3):1–8Google Scholar
- Christiaan HV, Ruud O, Elsebet N, James MC, Henrik HH, Lucianne G, Berend O, Naheed RM (2012) GABAA receptor a subunits differentially contribute to diazepam tolerance after chronic treatment. PLoS One 7(8):e3054Google Scholar
- Citraro R, Navarra M, Leo A, Donato Di Paola E, Santangelo E, Lippiello P, Aiello R, Russo E, De Sarro G (2016) The anticonvulsant activity of a flavonoid-rich Extract from Orange juice involves both NMDA and GABA-benzodiazepine receptor complexes. Molecules 21. doi: 10.3390/molecules21091261
- Gatta E, Cupello A, Di Braccio M, Grossi G, Robello M, Scicchitano F, Russo E, De Sarro G (2016) Anticonvulsive activity in Audiogenic DBA/2 mice of 1,4-benzodiazepines and 1,5-benzodiazepines with different activities at cerebellar granule cell GABAA receptors. J Mol Neurosci: MN 60:539–547. doi: 10.1007/s12031-016-0838-0 CrossRefPubMedGoogle Scholar
- Gregory SK (2011) Quercetin. Alter Med Rev 16(2):172–194Google Scholar
- Jarogniew JŁ, Aleksandra W, Ewa M, Dominika P, Dariusz D, Magdalena F (2012) Isobolographic characterization of interaction of levetiracetam with clobazam in the mouse 6 Hz psychomotor seizure model. J Pre-Clin Res 6(1):25–30Google Scholar
- Kothavade PS, Bulani VD, Nagmoti DM, Deshpande PS, Gawali NB, Juvekar AR (2015) Therapeutic Effect of Saponin Rich Fraction of Achyranthes aspera Linn. On Adjuvant-Induced Arthritis in Sprague-Dawley Rats. Autoimm Dis 2015:943645Google Scholar
- Magdalena FL, Aleksandra W, Maria WKW, Piotr T, Jarogniew JL (2014) Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model. J Neural Transm 121(7):707–715CrossRefGoogle Scholar
- Maria D, Arianna DL, Seyed FN, Zeliha ST, Seyed MN (2016) Polyphenols: well beyond the antioxidant capacity: Gallic acid and related compounds as neuroprotective agents: you are what you eat! Curr Pharm Biotechnol 15(4):362–372Google Scholar
- Marvin MG (2010) Overview of drugs used for epilepsy and seizures etiology, diagnosis, and treatment. PT 35(7):392–415Google Scholar
- Ndhlala AR, Ghebrehiwot HM, Ncube B, Aremu AO, Gruz J, Subrtova M (2015) Antimicrobial, anthelmintic activities and characterisation of functional phenolic acids of Achyranthes aspera Linn.: a medicinal plant used for the treatment of wounds and ringworm in East Africa. Front Pharmacol 6:274. doi: 10.3389/fphar.2015.00274 CrossRefPubMedPubMedCentralGoogle Scholar
- OECD (2001) Guideline on acute oral toxicity (AOT) Environmental health and safety monograph series on testing and adjustment No.425. http://www.oecd.org/chemicalsafety/risk-assessment/1948378.pdf. Accessed 23 Aug 2016
- Sasso O, La Rana G, Vitiello S, Russo R, D'Agostino G, Iacono A, Russo E, Citraro R, Cuzzocrea S, Piazza PV, De Sarro G, Meli R, Calignano A (2010) Palmitoylethanolamide modulates pentobarbital-evoked hypnotic effect in mice: involvement of allopregnanolone biosynthesis. Eur Neuropsychopharmacol 20(3):195–206CrossRefPubMedGoogle Scholar
- Saurabh SPS, Jha KK, Mishra G, Shruti S, Karchuli MS, Khosa RL (2011) Diuretic activity of whole plant extract of Achyranthes aspera Linn. Eur J Exp Biol 1(2):97–102Google Scholar
- Sean DH, Amanda N, Dana AH, Jan KM, Gary KH (2012) Benzodiazepine dependence and its treatment with low dose flumazenil. Br J Clin Pharmacol 77(2):285–294Google Scholar
- Suher MA, Abdullah SE, Saleem SA, Samir FS, Amina SA (2000) Effects of acute and chronic triazolam treatments on brain GABA levels in albino rats. Acta Neurobiol Exp (Wars) 60(4):447–455Google Scholar