Ameliorative potential of Colebrookea oppositifolia methanolic root extract against experimental models of epilepsy: Possible role of GABA mediated mechanism
Introduction
The scope of plant based medicines in the treatment of neurological diseases has been increasing enormously due to their wide therapeutic efficacy and greater levels of safety margin compared to synthetic class of drugs [1], [2]. In support of this many plant based medicines such as Swertia corymbosa [3], Coriandrum sativum [4], [5], Carum Carvi L. [6], Kalanchoe pinnata Lam. [7], Abies webbiana Lendl. [8], Laggera Aurita Linn. [9], Platonia insignis Mart. [10], and Dodonaea viscosa Linn [11] have been scientifically proved to possess potent anticonvulsant activity against experimental models of epilepsy. Epilepsy is a serious neurological disease affecting more than 65 million population worldwide, and each year approximately 0.2 million people are newly diagnosed with epilepsy [12], and it is estimated that close to 1 million deaths occur every year due to epilepsy [13], [14]. Currently various synthetic drugs are available for the treatment of epilepsy [15]. However, all the presently available synthetic anticonvulsant drugs are prone to cause one or more side/adverse effects like ataxia, mental confusion, sleep disturbance, anorexia, impotence, dizziness, mental slowing, impaired concentration, somnolence, aggression and so on [16], [17], [18]. Despite of copious efforts currently there is no safer and potent drug available for the treatment of epilepsy. In this context, there is an incredible scope for development of safe and potent drug for the management of epilepsy, in these lines plant based medicines are scientifically well proved for their better efficacy and also got a better edge over synthetic drugs, thus many researchers are focusing on herbal medicines to discover better and safe medicine for epilepsy [2]. In view of this, Colebrookea oppositifolia Smith (Lamiaceae), has been extensively used in the folklore medicine for the treatment of various diseases such as dermatitis, dysentery, fever, headache, peptic ulcer, hemostatic, wounds, as anti-fertility agent, fungicide, and the roots of the plant has been most widely used for the treatment of epilepsy [19], [20], [21], [22]. In line with its potential usage in folk medicine, various parts of the plant has been scientifically proven for anti-fertility [23], [24], antimicrobial [25], [26], antioxidant, [27], [28], antiulcer [29], and cardioprotective [30] activities. Additionally, relevant to the present work, various parts of Colebrookea oppositifolia is being extensively used for the treatment of epilepsy by various folk medicine practicing communities such as nomadic Gujjars, Tharu and Bhoxa in sub-Himalayan regions of India, from many decades and even now [31]. However, there is a paucity of scientific literature to support the anticonvulsant activity of the plant, therefore in the present study, we thought to evaluate the root extracts of Colebrookea oppositifolia for their possible anticonvulsant activity against experimental models of epilepsy.
Section snippets
Drugs and chemicals
Phenytoin was purchased from Sun Pharma (Mumbai, India), diazepam and flumazenil was procured from Ranbaxy (New Delhi, India), and pentylenetetrazole was purchased from Sigma-Aldrich (Bangalore, India). All the liquid chromatography (HPLC) grade solvents used in this study were procured from Merck Ltd. (Mumbai, India). All other chemicals and reagents used were of analytical grade and were purchased from HiMedia Laboratories Pvt. Ltd. (Mumbai, India)
Collection of plant material
The roots of Colebrookea oppositifolia were
Extraction of plant material
The extractive values of petroleum ether (PeCO), methanol (MeCO) and aqueous (AeCO) extracts were found to be 0.10, 3.45, and 2.73% w/w (gram by gram) respectively.
Acute oral toxicity study
Acute oral toxicity study for the plant extracts were performed as per OECD guidelines no. 425 up and down procedure. In acute toxicity studies PeCO showed central nervous system stimulation, at 550 mg/kg and higher doses exhibited clonic-tonic convulsions and death. However, MeCO and AeCO showed mild sedation and respiratory
Discussion
In this study root extracts of Colebrookea oppositifolia were assessed for antiepileptic activity in three different experimental models, namely six-hertz-seizure test, MES and PTZ models in mice.
As per the recommendations of recent anticonvulsant drug discovery program, all the extracts of Colebrookea oppositifolia (PeCO, MeCO and AeCO) were initially evaluated against six-hertz-seizure test in mice [46]. In fact, six-hertz-seizure test resembles the clinical state of limbic or partial
Conclusion
These findings demonstrate that, MeCO possess significant anticonvulsant activity, additionally MeCO showed a significant increase in GABA levels in the brain, and interestingly, the anticonvulsant action of MeCO was abolished by flumazenil, and thus confirmed that one of the possible mechanism/s behind the anticonvulsant activity of MeCO may be mediated through GABAergic pathway. Furthermore, in NMDA-induced lethality test the MeCO has showed partial protection, and thus confirmed the
Conflicts of interest
The authors declare there are no conflicts of interest.
Acknowledgements
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 the scientific and technical help provided by Ms.Vittartha Life Sciences, Bommasandra Industrial Area, Bangalore. We would like to thank Ms. Radiant Research Services Pvt Ltd., Bangalore, and Manipal college of Pharmaceutical sciences, Manipal for providing all the necessary facilities to
References (67)
- et al.
Anticonvulsant activity of methanolic extract from Kalanchoe pinnata Lam. stems and roots in mice: a comparison to diazepam
Neurologia
(2016) - et al.
Anticonvulsant properties of methanol leaf extract of Laggera Aurita Linn. F. (Asteraceae) in laboratory animals
J. Ethnopharmacol.
(2016) - et al.
GABA(A) receptor modulation and neuropharmacological activities of viscosine isolated from Dodonaea viscosa (Linn)
Pharmacol. Biochem. Behav.
(2015) - et al.
Antifertility studies of Colebrookia oppositifolia leaf extract in male rats with special reference to testicular cell population dynamics
Fitoterapia
(2001) - et al.
Ethnomedicinal plants used for treating epilepsy by indigenous communities of sub-Himalayan region of Uttarakhand, India
J. Ethnopharmacol.
(2013) - et al.
Influence of caffeine on the protective activity of gabapentin and topiramate in a mouse model of generalized tonic-clonic seizures
Pharmacol. Rep.: PR
(2016) - et al.
Hypnotic, anticonvulsant and muscle relaxant effects of Rubus brasiliensis. Involvement of GABA(A)-system
J. Ethnopharmacol.
(2000) - et al.
Anticonvulsant activity of AMPA/kainate antagonists: comparison of GYKI 52466 and NBOX in maximal electroshock and chemoconvulsant seizure models
Epilepsy Res.
(1993) - et al.
Isobolographic characterization of interactions of levetiracetam with the various antiepileptic drugs in the mouse 6 Hz psychomotor seizure model
Epilepsy Res.
(2009) Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs
Seizure
(2011)
Antiepileptic drug treatment strategies in neonatal epilepsy
Prog. Brain Res.
Safety and efficacy of flumazenil in the reversal of benzodiazepine-induced conscious sedation. The Flumazenil Pediatric Study Group
J. Pediatr.
Molecular mechanisms of antiseizure drug activity at GABAA receptors
Seizure
Comparison of in vivo and ex vivo [3H]flumazenil binding assays to determine occupancy at the benzodiazepine binding site of rat brain GABAA receptors
Neuropharmacology
N-methyl-d-aspartic acid-induced lethality in mice: selective antagonism by phencyclidine-like drugs
Brain Res.
Herbal medicine in the United States: review of efficacy, safety, and regulation: grand rounds at University of California, San Francisco Medical Center
J. Gen. Intern. Med.
A review of traditional plants used in the treatment of epilepsy amongst the Hausa/Fulani tribes of northern Nigeria, African
J. Traditional Complement. Altern. Med.
Evaluation of anticonvulsant, sedative, anxiolytic, and phytochemical profile of the methanol extract from the aerial parts of Swertia corymbosa (Griseb.) wight ex C.B. Clarke
BioMed Res. Int.
The effects of different fractions of Coriandrum sativum on pentylenetetrazole-induced seizures and brain tissues oxidative damage in rats
Avicenna J. Phytomed.
Effects of hydroalcoholic extract of Coriandrum sativum on oxidative damage in pentylenetetrazole-induced seizures in rats
Iran. J. Neurol.
Anticonvulsant effect of the aqueous extract and essential oil of carum carvi L. seeds in a pentylenetetrazol model of seizure in mice
Iran. J. Med. Sci.
Screening of methanol extract and ethyl acetate fraction of abies webbiana lindl. for neuropharmacological activities
Indian J. Pharm. Sci.
Evaluation of possible antioxidant and anticonvulsant effects of the ethyl acetate fraction from Platonia insignis Mart. (Bacuri) on epilepsy models
Epilepsy Behav.: E&B
Epilepsy, antiepileptic drugs, and aggression: an evidence-Based review
Pharmacol. Rev.
An unknown quantity–the worldwide prevalence of epilepsy
Epilepsia
Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984
Epilepsia
Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment, P & T
Peer- Rev. J. Formul. Manage.
Third generation antiepileptic drug monotherapies in adults with epilepsy
Expert Rev. Neurother.
The effect of epilepsy and antiepileptic drugs on sexual, reproductive and gonadal health of adults with epilepsy
Expert Rev. Clin. Pharmacol.
Sexual dysfunction related to antiepileptic drugs in patients with epilepsy
Expert Opin. Drug Saf.
Distribution, use pattern and prospects for conservation of medicinal shrubs in Uttaranchal state India
J. Mt. Sci.
Indian Material Medica
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2018, Journal of EthnopharmacologyCitation Excerpt :Lamiaceae) has been extensively used in the traditional system of Indian medicine for the treatment of various ailments such as headache, fever, dysentery, peptic ulcer, dermatitis, wounds, hemostatic, antifungal, as anti-fertility agent, and the roots of the plant has been most widely used for the treatment of epilepsy (NadkarnI, 1976; Kritikar and Basu, 2007). In support of potential medicinal uses in folk medicine, various parts of C. oppositifolia have been shown to possesses pharmacological activities such as anticonvulsant (Viswanatha et al., 2017), antioxidant (Riaz et al., 2011; Subba and Basnet, 2014), antiulcer (Ghaisas et al., 2010), antimicrobial (Subba and Basnet, 2014), cardioprotective (Pallab et al., 2011) and anti-fertility (Gupta et al., 2001) activities. Furthermore, confined to the present work, various parts of the plant such as roots, leaves and stem (in the form of decoction and dry powder) are being extensively used for the treatment of epilepsy by various folk medicine practicing communities such as nomadic Gujjars, Tharu and Bhoxa in sub- Himalayan regions of India, from many decades and even now (Sharma et al., 2013).
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