Anti-convulsant assessment: preliminary evaluation of three medicinal plants growing in Bayelsa State

Alade GO1*, James KO2, Ajibesin KK1
1Department of Pharmacognosy & Herbal Medicine, Faculty of Pharmacy, Niger Delta University, Wilberforce Island, Nigeria.
2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Wilberforce Island, Nigeria.
*Correspondence: Gideon O. Alade; aladegideon@yahoo.com, gideonalade@ndu.edu.ng

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Abstract

Background: In Bayelsa, several plants are used in the treatment of convulsion, pain and mental illness; however, there is paucity of information on the neuropharmacological effects of these plants.
Objective: To evaluate the anticonvulsant effects of Sansevieria liberica Gérôme & Labroy, Artocarpus altilis (Parkinson) Fosberg and Allophylus africanus P.Beauv.
Materials and Methods: The whole plant of Sansevieria liberica Gérôme & Labroy (Asparagaceae) and the leaves of Artocarpus altilis (Parkinson) Fosberg (Moraceae), and Allophylus africanus P.Beauv. (Sapindaceae) were macerated in 50% ethanol. Using known procedure, anticonvulsant activity was assessed on the extracts at doses ranging from 200 to 1000 mg/kg based on their LD50 values. Normal saline and diazepam were used as control and reference drug, respectively. The phytochemical screening was also carried out on the extract of each plant.
Result: Sansevieria liberica showed the most significant anticonvulsant effect against Pentylenetetrazol induced seizures in a dose dependent manner (50 mg/kg, 100mg/kg and 200mg/kg), while Artocarpus altilis gave the least anticonvulsant activity, showed no statistical significance when compared with normal saline group and showed no pharmacological similarity with the standard group, diazepam. Saponins were detected in all the three plant extracts.
Conclusion: The ethanol extracts of the plant materials in this study suggest antiseizure potential.

Keywords: Epilepsy, Anticonvulsant, Medicinal plants, Seizures, Phytoconstituents.

Cite this article: Alade GO, James KO, Ajibesin KK. Anti-convulsant assessment: preliminary evaluation of three medicinal plants growing in Bayelsa State. Yen Med J. 2022;4(2):20–27

INTRODUCTION

Convulsion is well known to be a neuro-electrical imbalance especially in the elevated status causing muscle rhythm incomprehension depending on the affected brain center or portion, presenting  many signs and symptoms including lack of awareness; loss of consciousness; eyes rolling back in the head; face that appears red or blue; changes to breathing; stiffening of the arms, legs, or whole body; jerky movements of the arms, legs, body, or head; lack of control over movements; inability to respond among others.1

The medical word convulsion is often referred to as seizure but it is not every epileptic seizure that can lead to convulsion, and it is not every convulsion that is caused by epileptic seizures. A wide array of phenomena may resemble epileptic seizures. Most children that are often given referral to tertiary hospitals because of “fits, faints and funny turns” do not eventually have epilepsy.2 Epileptic seizure is defined as “a temporary phenomenon of signs and/or symptoms which results from an unusual immoderate or synchronous neuronal activity in the brain.3 It can happen in a person who has no diagnosis of epilepsy such as found in injury involving the head, overdose of drugs or high fever in children.3

Epilepsy can develop at any age. Approximately half of new epilepsy cases start in infancy and adolescence (mainly in early months after birth). A lot of these persons tend to undergo a decline in the severity and rate of occurrence of seizures as they advance in age.4 However, some studies have reported an acute surge in seizure incidence as they advance in age. For instance, almost a quarter of fresh seizure cases can occur beyond 60 years of age.4

About 30% of seizures relate to a clear-cut abnormality in the brain.5 In the other 70% of cases the brain appears normal5 and in these cases, genetic causes are suspected. Multiple genes are however involved, and inheritance does not follow simple Mendelian rules.5

Many seizures can be managed by anti-seizure medications, sometimes called anti-convulsants or anti-epileptic drugs.  Different types of seizures require different medication management.6 Approximately 70% of seizures is successfully controlled with one anti-epileptic medication, while the remaining 30% are thus far resistant to medications.7

There is therefore a serious need to explore new and effective drugs from medicinal plants which have been an important source of safe and efficacious medicines.8 Some plants are used among some communities in Bayelsa State to manage convulsion. Sansevieria liberica Gérôme & Labroy, belongs to the family Asparagaceae. It is commonly called Bowstring hemp or Mother-in-laws tongue and also known as “Moda” (Hausa), “Ebubage” (Igbo), and “Ijo-ikoko” (Yoruba).9 Artocarpus altilis (Parkinson) Fosberg belongs to the family Moraceae and it is commonly referred to as breadfruit.10 Allophylus africanus P.Beauv. of the family Sapindaceae is usually a shrub, but sometimes a tree about 10 m tall.11

Ethnomedicinal uses

In Nigeria, the leaf of S. liberica is employed in ethnomedicine for treating asthma, abdominal pains, colic, diarrhea, eczema, gonorrhea, hemorrhoids, hypertension, menorrhagia, sexual weakness, snake bites and wounds of the foot, among others.12 The intact leaf of A. altilis or its latex is employed for massaging in cases of fractures, bruises, sprains, abscesses, thrush, diarrhoea, dysentery, stomach-ache, ear infections, muscle relaxant in cases of convulsive spasms and high blood pressure.13 The leaf of A. africanus is used for headache, migraine, malaria (Nigeria), colic, fever (Sierra Leone), conjunctivitis (Senegal)11 and convulsion (Oral report).

Biological activities

Sedative and anticonvulsant activities of the root,14 antioxidant and antimalarial,12 antimicrobial,15 hepatoprotective16 effects have been reported for S. liberica. Antimicrobial,17 alpha glucosidase inhibitory,18 larvicidal,19 antihelmintic20 and growth inhibitory21 activities have been reported for A. altilis. There are reports of A. africanus possessing antihepatotoxic,22 antimicrobial11 and anti-protective23 activities.

Chemical Constituents   

Screening of S. liberica for phytochemicals revealed the presence of fats and oils, flavonoids (catechin and flavone), saponins, proteins, steroids, terpenoids, tannins, carotenoids, alkaloids and glycosides.16 Artocarpus altilis contains phytoconstituents like stilbenes, arylbenzofuran, flavanone, flavones, triterpenes, sterols.24 The existence of alloeudesmenol, hanocokinoside, allotaraxerolide, and alloaminoacetaldehyde, tigmastane-3β,4β-diol and pinitol were reported in A. africanus.25

The objective of this study is to evaluate the anticonvulsant effects of Sansevieria liberica Gérôme & Labroy, Artocarpus altilis (Parkinson) Fosberg and Allophylus africanus P.Beauv.

MATERIALS AND METHODS

Study design and setting

The study is of an experimental type, conducted in the Pharmacognosy & Herbal Medicine and Pharmacology laboratories, both in the Faculty of Pharmacy, Niger Delta University, Wilberforce Island, Bayelsa State, South of Nigeria.

Plant Collection and Identification

Three (3) plants (Sansevieria liberica Gérôme & Labroy, Artocarpus altilis (Parkinson) Fosberg and Allophylus africanus P.Beauv.) were sourced from Bayelsa State. Each plant sourced was identified at site by a local guide in their respective locations as presented in Table 1. Authentication of the plants was done by Dr. A.T Oladele of the Department of Forestry and Wildlife Management University of Port Harcourt, Nigeria. Voucher specimens were deposited in the Herbarium Unit of the Department of Pharmacognosy & Herbal Medicine, Niger Delta University, Wilberforce Island, Bayelsa State. The voucher specimen numbers are as presented in Table 1. The various plant parts were thereafter collected.

 

 

Table 1: Location and Collection of Plants

Plant

Location

Part collected

Date of collection

Herbarium Number

Sansevieria liberica Gérôme & Labroy

Main campus, Niger Delta University Wilberforce Island, Bayelsa State.

Whole plant

February, 2018

NDUP 126

Artocarpus altilis(Parkinson) Fosberg

Okaka, Yenagoa, Bayelsa state.

Leaves

January, 2018

NDUP 122

Allophylus africanus P.Beauv

Ogobiri town, Bayelsa state.

Leaves

March, 2018

NDUP 121

 

 

Extraction of plant materials

The plant materials were oven-dried at temperature between 35 and 40˚C and pulverized subsequently. The plant powder (300 g) was macerated using 50% ethanol for 72 h with periodic agitation. The filtered liquid extract was then concentrated to dryness in vacuo at 30˚C to obtain dried extracts. The percentage yield was estimated. The extracts were stored at 4˚C in a refrigerator prior to use.

Phytochemical Screening

Phytochemical screening was carried out on the crude ethanol extracts of the three plants to determine the classes of constituents each plant contains using standard procedure as described by Sofowora.26

Dose Preparation

The individual doses of the plant extracts were estimated, guided by their respective LD50 values ranging from 0.37 – 4.57 g/kg. Thus, three doses per plant extract with the values ranging from 200, 400, 600, 800 to 1000 mg/kg were used according to the LD50 value of the affected plant extract.

Experimental Animals

Mice were sourced from the Research and Animal Breeding Unit of Pharmacology and Toxicology Department, Faculty of Pharmacy Niger Delta University, Wilberforce Island, Bayelsa State. The animals acclimatized for 7 days and were handled according to the principles of laboratory animal care as required by the National Institute of Health-NIH (publication No 85-23) guideline and procedures.27 Ethical approval to carry out the work was obtained from the Ethical committee of the Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Wilberforce Island, Bayelsa State, Nigeria.

Pentylenetetrazol (PTZ) Model

Pentylenetetrazol (PTZ) is a chemoconvulsant popularly employed in seizure induction.28 Overnight fasted mice having free access to water until 1h before the experiment were weighed and randomly allotted into 11 groups (n = 5).

Group 1: received normal saline 10 ml/kg per ora (p.o) and served as control.

Groups 2 – 4 received 200, 400 and 800mg/kg of extract of S. liberica, respectively.

Groups 5 – 7 received 400, 800 and 1000mg of extract of A. altilis, respectively.

Groups 8 – 10 received 400, 800 and 1000mg of extract of A. africanus, respectively.

Group 11 received diazepam 5 mg/kg intraperitoneally (I.P) and served as standard. 

Pentylenetetrazol 85mg/kg (I.P) was administered to all the groups 30 min after the various treatments and the animals were observed for 30 min for the onset of convulsions (tonic- clonic, hind limb extensions). The number of animals that convulsed and the degree of protection offered by the extract were compared with those of the control and standard drug (diazepam). The delay in onset of convulsions indicated anticonvulsant activity.

Data Analysis

The results were analysed using Graph Pad Prism 7. The outcome measures are expressed as mean ± standard error of mean (SE). Mean comparisons were done using one-way analysis of variance (ANOVA), followed by multiple comparison post hoc Dunnet test. Differences between the groups were considered significant at P < 0.05.

 

 

RESULTS

Phytochemical Screening

The various plants showed relative variations in their phytochemical compositions as indicated in Table 2.

Table 2: Phytochemical constituents of the medicinal plants studied

Medicinal Plants

Alkaloids

Tannins

Saponins

Cardiac glycosides

Anthraquinones

      S. liberica

      +

     _

      +

             +

           _

A.      Altilis

      +

     +

      +

             _

           _

A.      Africanus

      _

     +

      +

             _

           _

 + indicating “positive” and – indicating “negative”

Anticonvulsant Evaluation

The anticonvulsant effects of the different plant species studied are presented in the following tables

Table 3: Onset and duration of seizure effects of S. liberica

Treatment

Dose

Latency of seizure (s)

Duration of seizure (s)

NS

10 ml/kg

   5.2±0.4

     19.0±1.4

SLE

200 mg/kg

   86.6±16.4**

     1123.0±143.9

SLE

400 mg/kg

   81.8±14.5**

     552.4±59.6

SLE

800 mg/kg

   69.0±14.0*

     403.6±558.2

DZP

5.0 mg/kg

   175.4±22.0****

     1645.0±7.0

Data showing anticonvulsant activity using ANOVA multiple comparison post hoc dunnet test. * Signifies P ˂ 0.05. NS=Normal Saline; SLE= Sansevieria liberica Extract; DZP=Diazepam; S = Second.

Graph showing antiseizure potential using ANOVA multiple comparison post hoc dunnet test. * Signifies P ˂ 0.05. NS = Normal Saline; DZP = Diazepam; S = Second

Figure 1: Anticonvulsant effects of S. liberica

Table 4: Onset and duration of seizure effects of A. altilis

Treatment

Dose

Latency of seizure (s)

Duration of seizure (s)

NS

10 ml/kg

  5.2±0.4

    19.0±1.4

ARTE

400 mg/kg

  40.0±2.2

    157.0±54.8

ARTE

800 mg/kg

  39.0±2.5

    176.2±71.3

ARTE

1000 mg/kg

  42.2±5.2

    444.4±174.0

DZP

5.0 mg/kg

  175.4±22.0****

    1645.0±7.0

Data showing anticonvulsant activity using ANOVA multiple comparison post hoc dunnet test. * Signifies P ˂ 0.05. NS = Normal Saline; ARTE= Artocarpus altilis Extract; DZP = Diazepam; S = Second.

Graph showing antiseizure potential using ANOVA multiple comparison post hoc dunnet test. * Signifies P ˂ 0.05. NS= Normal Saline; DZP = Diazepam; S = second

Figure 2: Anticonvulsant effects of A. altilis

 

Table 5: Onset and duration of seizure effects of A. africanus

Treatment

Dose

Latency of seizure (s)

Duration of seizure (s)

NS

10 ml/kg

    5.2±0.4

       19.0±1.4

AAE

400 mg/kg

    52.6±1.4*

       311.6±23.1

AAE

800 mg/kg

    60.6±2.6**

       80.4

AAE

1000 mg/kg

    61.0±7.2**

       540.8±98.5

DZP

5.0 mg/kg

    175.4±22.0****

       1645.0.0±7.0

 

Data showing anticonvulsant activity using ANOVA multiple comparison post hoc dunnet test. * Signifies P ˂ 0.05. NS= Normal Saline; AAE = Allophylus africanus Extract; DZP = Diazepam; S = Second.

Graph showing antiseizure potential using ANOVA multiple comparison post hoc dunnet test. * Signifies P ˂ 0.05. NS = Normal Saline; DZP = Diazepam; S = Second.

Figure 3: Anticonvulsant effects of A. africanus

 

DISCUSSION

Phytochemical screening of the three plants revealed the presence of different classes of constituents, they include glycosides, tannins, saponins, alkaloids, and anthraquinones in the ethanol extracts of the plants used in this study (Table 2). Saponins, followed by alkaloids and tannins were found in the three plants. Saponins have been reported to exhibit anticonvulsant activity.29-32 Alkaloids are also known to be effective anticonvulsants in medicinal plants.29

Pentylenetetrazol (PTZ) exerts its convulsant effects by inhibiting the activity of gamma amino butyric acid (GABA) at GABA receptors.33 The augmentation of GABA neurotransmission lessens episode of convulsions and vice versa.34 One of the famous drug used in seizure control; diazepam, potentiates GABA.35 The rats that were pretreated with diazepam (5 mg/kg, I.P) did not elicit any episode of convulsion as expected neither was there mortality when treated with PTZ.

The plant species studied gave varying degrees of anticonvulsant activities. The biological evaluation of anticonvulsant properties is centered on delayed onset rather than other parameters of anticonvulsant evaluation in all the medicinal plants studied in this work.

The anti-seizure screening of S. liberica is pharmacologically responsive in increasing the latency of seizure in dose dependent order (Table 3), but the response manner is in reverse of the dose order as observed in figure 1. This result at the administered doses showed statistical significance. It is worthy of note that the order of pharmacological response in this plant extract only suggests higher response in lower concentration which is pharmacologically possible and explainable by the dose/response evaluations and drug assay contexts.

The evaluation of anticonvulsant property of A. altilis showed no statistical significance when compared with the normal saline group and showed no pharmacological similarity with the standard group; diazepam (Table 4, Figure 2).

The evaluation of A. africanus for its anticonvulsant property proved relatively potent in a dose dependent manner without statistical significance among the studied doses when compared with normal control (Table 5, Figure 3). Like A. africanus, no study has proven anticonvulsant potential property as at the time of this study. 

From the result, most of the medicinal plant extracts showed increased latency of seizure observed to be statistically significant when compared with normal saline group. Considering the pharmacological mechanism of action of the standard drug, diazepam, it potentiates gamma amino butyric acid sub type A receptor (GABAA) to reflect its anticonvulsant potential. In like manner, these plant extracts have relatively shown anticonvulsant potentials by mimicking diazepam but one thing that is not yet clear about the activity of the plant extracts is whether or not they are affecting Reticular Activating System (RAS) region of the brain that may reflect hypnotic and sedative properties of the plants. This work is a step towards validating the use of A. atilis and A. africanus in ethnomedicine while the leaf of S. liberica whose root has been reported earlier as an anticonvulsant is also found to be a potential anticonvulsant from this study. 

CONCLUSION

The study shows the anticonvulsant potentials of the leaves of S. liberica and A. africanus.  The study has thus supported their use in traditional medicine in Bayelsa State. These plants can be utilized in drug discovery of effective anticonvulsant.

ACKNOWLEDGEMENT

The authors are grateful to Mr. GS Uwakwe, the Chief Technologist in the Department of Pharmacognosy & Herbal Medicine, Faculty of Pharmacy, Niger Delta University, Wilberforce Island, Bayelsa State, for preparing the laboratory environment for this work.

CONFLICT OF INTEREST

The authors have no conflicts of interests.

 

AUTHOR CONTRIBUTIONS

GOA and KKA contributed to the conception, design and plant collection. KOJ, GOA and KKA conducted the bench work. GOA wrote the manuscript while KKA edited it. All authors read and approved the final draft of the manuscript.

ETHICAL CONSIDERATIONS

Ethical approval to carry out the work was obtained from the Ethical committee of the Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Wilberforce Island, Bayelsa State, Nigeria.

REFERENCES

  1. Kemelayefa OJ, Kagbo H. Anticonvulsant Potential of Dichloromethane Extract of Aspilia africana leaf in mice. J Pharm Res Int. 2019;25(4):1-10.
  2. Hindley D, Ali A, Robson C. Diagnoses made in secondary care “fits, faints and funny turns” clinic. Arch Dis Child. 2006;91(3):214-218.
  3. Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). 2005;46(4):470-472. doi: 10.1111/j.0013-9580.2005.66104. x.
  4. WHO, Seizure fact sheet. 2019. Available from https://www.who.int/news-room/fact-sheets/detail/epilepsy. Accessed February 9, 2022.
  5. Stafstrom CE, Carmant L. Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Med .2015;5(6):a022426.
  6. Wahab A. Difficulties in Treatment and Management of Epilepsy and Challenges in New Drug Development. Pharmaceuticals (Basel). 2010;3(7):2090-2110.
  7. Goldenberg MM. Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment. P T. 2010;35(7):392-415.
  8. Sofowora A, Ogunbodede E, Onayade A. The role and place of medicinal plants in the strategies for disease prevention. Afr J Tradit Complement Altern Med. 2013;10(5):210-229.
  9. Rukaiyat M, Garba S, Labaran S. Antimicrobial activities of hexacosane isolated from Sanseveria liberica (Gerome and Labroy) plant. Adv Med Plant Res. 2015;3(3):120-125.
  10. Sikarwar MS, Hui BJ, Subramaniam K, Valeisamy BD, Yean LK, Balaji K. A Review on Artocarpus altilis (Parkinson) Fosberg (breadfruit). J App Pharm Sci. 2014;4(08):091-097.
  11. Ferreres F, Gomes NGM, Valentão P, Pereira DM, Gil-Izquierdo A, Araújo L, Silva TC, Andrade PB. Leaves and stem bark from Allophylus africanus Beauv.: An approach to anti-inflammatory properties and characterization of their flavonoid profile. Food Chem Toxicol. 2018;118:430-438. doi: 10.1016/j.fct.2018.05.045.
  12. Orabueze IC, Uzor SC, Ndiaye B, Uba D, Ota DA, Agbedahusi J. Antimalarial, Antioxidant Activities and Chemoprofile of Sansevieria libericaGerome and Labroy (Agavaceae) Leaf Extract. Adv Pharmacol Pharm Sci. 2021;2021:9053262.
  13. Luzuriaga-Quichimbo CX, Blanco-Salas J, Ceron-Martinez CE, Rulz-Tellex T. Providing added value to local uses of paparahua (Artocarpus atilis) in Amazonian Ecuador by phytochemical data review. bras. farmacogn. 2019;29(1):62-68.
  14. Adeyemi OO, Yemitan OK, Adebiyi OO. Sedative and anticonvulsant activities of the aqueous root extract of Sanseviera liberica Gerome & Labroy (Agavaceae). J Ethnopharmacol. 2007;113(1):111-114.
  15. Ikewuchi CC, Ikewuchi CJ, Ayalogu OE, Onyeike NE. Proximate and Phytochemical Profile of Sansevieria liberica Gérôme and Labroy. J Appl Sci Environ Manage. 2010;14(2):103 – 106.
  16. Ikewuchi JC, Ikewuchi CC, Igboh NM, Mark-Balm T. Protective effect of aqueous extract of the rhizomes of Sansevieria liberica Gérôme and Labroy on carbon tetrachloride induced hepatotoxicity in rats. EXCLI J. 2011;10:312-321.
  17. Sivagnanasundaram P, Karunanayake KOLC. Phytochemical Screening and Antimicrobial activity of Artocarpus heterophyllus and Artocarpus altilis leaf and stem bark extracts. OUSL J. 2015;9:1-17.
  18. Rante H, Alam G, Irwan M. α –Glucosidase inhibitory activity of breadfruit leaf extract (Artocarpus altilis (parkinson) fosberg). J Phys: Conf Ser. 2019;1341(7): 072015.
  19. Famuyiwa FG, Kolawole EB. Larvicidal activity of Artocarpus altilis against Culex quinquefasciatus. Int J Plant Stud. 2019;2(1):1-4.
  20. Bhattacharya K, Bhattacharjee A, Chanu NR, Dey BK, Devi CM. Phytochemical screening and Anthelmintic activity of Artocarpus altilis Res J Pharm Technol. 2021;14(2):640-644. doi: 10.5958/0974-360X.2021.00114.1.
  21. Ikpefan EO. Preliminary Growth inhibitory studies of the methanol extract and fractions of leaves of Artocarpus altilis. J Sci Pract Pharm. 2018;5(2):275-280.
  22. Hoffmann-Bohm K, Lotter H, Seligmann O, Wagner H. Antihepatotoxic C-Glycosylflavones from the leaves of Allophyllus edulis edulis and gracilis. Planta Med. 1992;58:544-548.
  23. Biseko EZ, Swai HS, Mbugua RW, Ndunga JW, Chepnga J, Gathirwa JW. In vitro antiproliferative potential of Annona senegalensis and Allophylus africanus P. Beauv. Plant extracts against selected cancer cell lines. J. Med. Plant Res. 2019;13(13):304-311.
  24. Shamaun SS, Rahmani M, Hashim NM, Ismail H BM, Sukari MA, Lian GEC, et al. Prenylated flavones from Artocarpus altilis. J Nat Med. 2010;64(4):478–481.
  25. Oladosu IA, Balogun SO, Liu ZQ. Chemical constituents of Allophylus africanus. Chin J Nat Med. 2015;13(2):133-41. doi: 10.1016/S1875-5364(15)60017-6.
  26. Sofowora A. Screening Plants for Bioactive Agents. In: Medicinal Plants and Traditional Medicinal in Africa.2nd ed. Ibadan: Nigeria; Spectrum Books Ltd: 1993.; pp. 134–156. 
  27. Badyal DK, Desai C. Animal use in pharmacology education and research: the changing scenario. Indian J Pharmacol. 2014;46(3):257–265.
  28. Akula KK, Dhir A, Kulkarni SK. Effect of various antiepileptic drugs in a pentylenetetrazol-induced seizure model in mice. Methods Find Exp Clin Pharmacol. 2009;31(7):423-32. doi: 10.1358/mf.2009.31.7.1393610.
  29. Zhu H, Wan J, Wang Y, Li B, Xiang C, He J, et al. Medicinal compounds with antiepileptic/anticonvulsant activities. 2014;55(1):3-16.
  30. Singh D, Goel RK. Anticonvulsant mechanism of saponins fraction from adventitious roots of Ficus religiosa: possible modulation of GABAergic. bras. farmacogn.  2016;26:579–585.
  31. Singh D, Singh B, Goel RK Role of saponins for the anticonvulsant effect of adventitious roots of Ficus religiosa. Biol. 2012;50(7):816–822.
  32. Chindo BA, Anuka JA, McNeil L, Yaro AH, Adamu SS, Amos S, Connelly WK, Lees G, Gamaniel KS. Anticonvulsant properties of saponins from Ficus platyphylla stem bark. Brain Res Bull. 2009;78(6):276-282.
  33. Hansen SL, Sperling BB, Sánchez C. Anticonvulsant and antiepileptogenic effects of GABAA receptor ligands in pentylenetetrazole-kindled mice. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(1):105-113.
  34. Son HL, Yen PTH. Preliminary phytochemical Screening, Acute oral toxicity and anticonvulsant activity of the berries of Solanum nigrum Trop J Pharm Res. 2014;13(6):907-912.
  35. Isojärvi JI, Tokola RA. Benzodiazepines in the treatment of epilepsy in people with intellectual disability. J Intellect Disabil Res. 1998;42(1):80-92.
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