• 100 Views
  • 22 Downloads
ejbcp: Vol. 10
Research Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 10 (2020), Article ID 101381, 4 pages
doi:10.32527/2020/101381

Panax Ginseng Inhibits Maximal Electroshock Induced Convulsions in Mice

Hossam A. El Sisi1,2, Noha A. T. Abbas1, Ibrahim A. Awwad1, and Bander A. Alrasheedi2

1Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

2College Pharmacy, Qassim University, Saudi Arabia

Received 10 July 2018; Accepted 12 February 2019

Editor: Walter Müller

Copyright © 2020 Hossam A. El Sisi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Epilepsy is a serious common neurological disease. Panax ginseng root has been identified as a potential therapy for many disorders. The present study investigated the possible anticonvulsant activity of Panax ginseng on maximal electroshock (MES) induced seizure in mice. Mice were divided into the following groups: Group A (control group): injected with normal saline then exposed to electric shock. Group B (test group): injected with sodium valproate (300 mg/kg, 600 mg/kg, 900 mg/kg). Then exposed to electric shock. Group C (test group): injected with Panax Ginseng (150, 250, 350 mg/kg) then exposed to electric shock. All animals were examined for motor coordination on rotarod test. We concluded that P. ginseng at moderate and high doses significantly decreased the HLE duration of convulsion in mice, denoting that P. ginseng has anticonvulsant effects. the antiepileptic activity of P. ginseng might be due to its antioxidative actions, anti-inflammatory, its regulating effect on sodium ion channels and/or due to its possible modulation of GABA receptor channel activity for further investigations.

1. Introduction

Epilepsy is a serious common neurological disease. It usually leads to decreased quality of life with increased mortality and morbidity [1]. About 30% of patients with epilepsy do not respond well to the available antiepileptic drugs [2]. The use of classical and new antiepileptic agents is usually associated with increased incidence of adverse effects. Thus an important hope for many trails is to develop new anti-seizure agents with a good rate of success and less risk of side effects [3].

Panax ginseng root (Korean ginseng) is considered as one of the most valuable and widely used medicinal herb in Asian countries [4,5]. It has been identified as a potential therapy for many disorders including anti-stress, anxiolytic, Alzheimer's disease, cognitive impairment and dementia [6]. The goal of the present study is to screen the anticonvulsant activity of different doses of panax ginseng on maximal electroshock (MES) induced seizure in mice.

2. Material and Methods

2.1. Experimental animals

Adult male albino mice (weighting) (22-26 gm) were delivered from National Research Laboratory, College of Pharmacy Qassim University, Saudi Arabia, and kept in colony cages under standardized housing conditions and free access to tap water and food (Natural light-dark cycle, a temperature of 22±1C). After 5 days of adaptation to laboratory conditions, the animals were divided randomly to the experimental groups. All tests were performed between 8.00 and 15.00 h and each mouse was used once. The experimental protocol was approved by the Ethics Committee of College of Pharmacy, Qassim University, Saudia Arabia.

2.2. Drugs and chemicals

1. Panax ginseng (Ginsana capsule 100 mg).

2. Sodium valproate (Depakine 200 mg tablets), Sanofi Aventis

2.3. Maximal electroshock (MES) induced seizures test

A 50 HZ stimulus of 200 milliseconds duration was applied through saline wet ear electrode to improve electrode contact. Current intensity was increased in a step-wise manner from 1 to 30 MA to reach the current which causes convulsions without the death of the animals. 13 MA produced convulsions with tonic hind limb extension. This current was used throughout this study. The duration of seizure (i.e. hind limb tonic extension) following electroshock application to the mice was recorded.

2.4. Study design

Group A (control group): 18 mice were injected with normal saline then exposed to electric shock.

Group B (test group): 18 mice were injected with sodium valproate (300 mg/kg, 600 mg/kg, 900 mg/kg). Then exposed to electric shock.

Group C (test group): 18 mice were injected with Panax Ginseng (150, 250, 350 mg/kg), then exposed to electric shock.

Each group was divided into three equal groups 6/each.

2.5. Rodent shocker

The apparatus used in Rodent Shoker TYP 21 (Harved apparatus GmbH Germany).

2.5.1. Assessment of motor coordination in mice

The effects of drug administration on the motor coordination of mice can be detected by ROTARODS LE 8200 (Panlab, S.L Spain).

A central drum divided into sections for individual animals rotate from 4 to 40 revolutions per minute in 0.5 to 10 minutes, either at a constant speed or at a steady acceleration rat. The time, the animal spends from the beginning of the test until the animal falls from the drum in each section (TS) is taken as a measure of coordination [7].

2.5.2. Procedure

The acceleration time used in this study is 10 min. Before starting a test, the animals have to be trained for 3-4 days to be able to walk on Rotarod. To start a test, position the animals on their partitions on Rotarod, then adjust the run-stop button to the middle position and left the needed leavers, after that use the run-acceleration button to adjust the acceleration time then press a start-stop button. At this time, the speed and time counters will start to work. Once the animal fall, its counters will stop running [7].

2.6. Statistical analysis

The obtained variables were tabulated as mean± SD. Comparison between different groups was made using one way analysis of variance (one-way ANOVA) followed by post Hock (least significant difference) LSD tests as described by Armitage and Berry [8]. The difference was considered to be significant when P<0.05 statistical package of social science (SPSS) (version 16).

3. Results

The results of the present study showed that, in the MES induced seizure model, sodium valproate at low, medium and high doses (300, 600, 900 mg/kg) showed significant anticonvulsive effects which represented by significant reduction of the duration of hind limb extension in the animals compared with the control untreated group (table 1,2). Furthermore, panax ginseng at low dose administration (500 mg/kg) showed no anticonvulsant effect. However, in moderate and high doses (250 mg/kg & 350 mg/kg) respectively panax ginseng showed a significant reduction in the duration of hind limb extension in mice compared with the control untreated group (Table 1,2).

In the present study, P. ginseng showed significant improvement in motor coordination estimated using Rotarod as evident by the insignificant change in the rotarod performance test between the P. ginseng treated and the control values. Moreover, on general observation no eyelid ptosis, bristling fur, weeping eyes were observed in the P. ginseng treated group. (Table 2)

T1

Table 1: Comparison between the effects of Panax ginseng and Sodium valproate on the duration of hind limb extension in mice.

T2

Table 2: Comparison between the effect of Panax ginseng and sodium valperoate on muscle coordination in mice.

4. Discussion

In this study Panax ginseng (P. ginseng) different doses were evaluated against MES induced convulsion in mice. MES induced seizure test is a widely used test to determine the potential antiseizure effects of different substances in rodents [9]. In the present work, P. ginseng at moderate and high doses significantly decreased the HLE duration of convulsion in mice, denoting that P. ginseng has anticonvulsant effects. These results are inconsistent with Choi et al., [10] who demonstrated that, the Korean red ginseng exerts anticonvulsant action in mice against picrotoxin and bicuculline induced seizure via the change in the brain GABA and glutamate contents.

Gupta et al., [11] also demonstrated that P. ginseng induced antiepileptic effect against PTZ induced kindling in rats.

There are many types of ginseng available for medical use. The most popular are Panax quinquefolicus (American ginseng), Korean red ginseng and Panax ginseng (oriental ginseng). The active constituents vary according to the species [12].

The most active constituents of P. ginseng are ginsenoside Rb1, ginsenoside-Re, ginsenoside-Rd, and ginsenoside- Rg1 [13]. Seizures can be evoked by oxidative stress and free radicals accumulation under pathological conditions [14].

kabuto et al., [15] demonstrated that antioxidant administration showed protective efficacy against iron-induced epileptic discharges in rats.

Lim et al. [16] and Cantuti-Castelvetri et al. [17] showed that ginsenosides, the active components of P. ginseng, exerted potent antioxidant properties.

Zhou et al., [18] also demonstrated that ginsenoside-Re can improve mitochondrial function and reduce mitochondrial swelling via reduction of MDA brain content and up-regulation of the activity of superoxide dismutase.

Citraro et al. [19] demonstrated that, cyclooxygenase (Cox) which involved in the production of many Pro-inflammatory prostaglandins can play an important role in inflammation-induced seizure. Cox-2 in the brain reported to increase during and after seizures thus Cox-2 inhibitors able to reduce or even prevent the development of absence seizure in WAG/Rij rat [19].

de Oliveiraet al., [20] also showed that ginsenoside- Ro has an anti-inflammation action against muscle damaging.

Indeed P. ginseng targeted multiple points within the inflammatory cascade as it can inhibit inducible nitric oxide synthase (iNOS), cycloxygenase-2 (Cox-2) and nuclear factor kappa B [21]. Wang et al., [22] also demonstrated that, ginsenoside-Rb1 decreases expression of Cox-2 mRNA in brain tissue, reduces inflammation and nerve damage. They also showed that ginsenoside- Rg1 can improve memory and learning functions in rats, regulate cell survival and neurogenesis, and inhibit the activity of caspase 3.

Wang et al., [22] also showed that ginsenoside Rd can reduce oxidative and inflammatory damage, protect mitochondria and reduce cell apoptosis in a wide range of tissues.

Liu et al., [12] showed that the ginsenoside Rb-1 in P. ginseng has been shown to produce a neuroprotective action by blocking the sodium channels and it also has been shown to regulate GABAergic transmission Indeed MES induced seizures are sensitive to sodium channels blocking agents.

It can be concluded, from all of the previous works and our study that, the antiepileptic activity of P. ginseng might be due to its antioxidative actions, anti-inflammatory, its regulating effect on sodium ion channels and/or due its possible modulation of GABA receptor channel activity for further investigations.

Competing Interests

The authors declare no competing interests.

References

  1. Who, Epilepsy. Fact sheet No. 999 http://www.who.int/mediacentre/factsheets/fgs 999/en/.
  2. Gorter Ja and Ptschka H, (2012): Drug resistance. In: Neobles JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper’s Basic Mechanisms of the Epilepsies. 4th ed. Bethesda, MD: National Center for Biotechnology Information (US).
  3. Meir Bialer and H. Steve White, “Key factors in the discovery and development of new antiepileptic drugs,“ Nature Reviews Drug Discovery, vol. 9, no. 1, pp. 68–82, 2010. Publisher Full Text | Google Scholar
  4. Jeong-Hill Park, Hwa-Young Cha, Jeong-Ju Seo, Jin-Tae Hong, Kun Han, and Ki-Wan Oh, “Anxiolytic-like effects of ginseng in the elevated plus-maze model: Comparison of red ginseng and sun ginseng,“ Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 29, no. 6, pp. 895–900, 2005. Publisher Full Text | Google Scholar
  5. Thi Hong Van Le, Seo Young Lee, Tae Ryong Kim et al., “Processed Vietnamese ginseng: Preliminary results in chemistry and biological activity,“ Journal of Ginseng Research, vol. 38, no. 2, pp. 154–159, 2014. Publisher Full Text | Google Scholar
  6. Ik-Hyun Cho, “Effects of Panax ginseng in Neurodegenerative Diseases,“ Journal of Ginseng Research, vol. 36, no. 4, pp. 342–353, 2012. Publisher Full Text | Google Scholar
  7. Leal Mb, Souza Do, and Eusabetsky E, (2000): Long lasting lobogaine protection against NMDA induced convulsions in mice. Neurochem Res; 25: 1083-1087.
  8. Armitage P and Berry G, (1994): Statistical methods in medical research, 3rd edition, pp. 620. Blackwell Scientific Publications, Oxford, London.
  9. Wolfgang Löscher, Dagmar Hönack, Christian P Fassbender, and Björn Nolting, “The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. III. Pentylenetetrazole seizure models,“ Epilepsy Research, vol. 8, no. 3, pp. 171–189, 1991. Publisher Full Text | Google Scholar
  10. Choi J, Yoo Ym, and Park Hj, (2007): Inhibitory effects of the Korean Red Ginseng extract on the content of neurotransmitter related components of the mouse brain in convulsion induced model. Natural Product Sciences; 13 (4): 384-389.
  11. Gupta Yk, Sharma M, and Chaudhary G, (2001): Antiepileptic activity of Panax ginseng against pentylenetetrazole induced kindling in rats. Indian J Physiol Pharmacol; 45 (4): 502-506.
  12. Dong Liu, Bei Li, Yi Liu, Anoja S. Attele, John W. Kyle, and Chun-Su Yuan, “Voltage-dependent inhibition of brain Na+ channels by American ginseng,“ European Journal of Pharmacology, vol. 413, no. 1, pp. 47–54, 2001. Publisher Full Text | Google Scholar
  13. S.P. Li, C.F. Qiao, Y.W. Chen et al., “A novel strategy with standardized reference extract qualification and single compound quantitative evaluation for quality control of Panax notoginseng used as a functional food,“ Journal of Chromatography A, vol. 1313, pp. 302–307, 2013. Publisher Full Text | Google Scholar
  14. Annadora J. Bruce and Michel Baudry, “Oxygen free radicals in rat limbic structures after kainate-induced seizures,“ Free Radical Biology and Medicine, vol. 18, no. 6, pp. 993–1002, 1995. Publisher Full Text | Google Scholar
  15. Hideaki Kabuto, Isao Yokoi, and Norio Ogawa, “Melatonin Inhibits Iron-Induced Epileptic Discharges in Rats by Suppressing Peroxidation,“ Epilepsia, vol. 39, no. 3, pp. 237–243, 1998. Publisher Full Text | Google Scholar
  16. J.-H Lim, T.-C Wen, S Matsuda et al., “Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient of ginseng root,“ Neuroscience Research, vol. 28, no. 3, pp. 191–200, 1997. Publisher Full Text | Google Scholar
  17. Ippolita Cantuti-Castelvetri, Barbara Shukitt-Hale, and James A Joseph, “Neurobehavioral aspects of antioxidants in aging,“ International Journal of Developmental Neuroscience, vol. 18, no. 4-5, pp. 367–381, 2000. Publisher Full Text | Google Scholar
  18. Xiao-Mian Zhou, Ying-Lin Cao, and De-Qiang Dou, “Protective Effect of Ginsenoside-Re against Cerebral Ischemia/Reperfusion Damage in Rats,“ Biological & Pharmaceutical Bulletin, vol. 29, no. 12, pp. 2502–2505, 2006. Publisher Full Text | Google Scholar
  19. Rita Citraro, Antonio Leo, Rosario Marra, Giovambattista De Sarro, and Emilio Russo, “Antiepileptogenic effects of the selective COX-2 inhibitor etoricoxib, on the development of spontaneous absence seizures in WAG/Rij rats,“ Brain Research Bulletin, vol. 113, pp. 1–7, 2015. Publisher Full Text | Google Scholar
  20. Antonio C Cabral De Oliveira, Andrea C Perez, Gracia Merino, Julio G Prieto, and Ana I Alvarez, “Protective effects of Panax ginseng on muscle injury and inflammation after eccentric exercise,“ Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, vol. 130, no. 3, pp. 369–377, 2001. Publisher Full Text | Google Scholar
  21. Young-Sam Keum, Seong Su Han, Kyung-Soo Chun et al., “Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-κB activation and tumor promotion,“ Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, vol. 523-524, pp. 75–85, 2003. Publisher Full Text | Google Scholar
  22. Xumei Wang, Shaoxia Wang, and Limin Hu, “Neuroprotective effect of panax notoginseng saponins and its main components,“ World Journal of Neuroscience, vol. 04, no. 01, pp. 12–17, 2014. Publisher Full Text | Google Scholar
Research Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 10 (2020), Article ID 101381, 4 pages
doi:10.32527/2020/101381

Panax Ginseng Inhibits Maximal Electroshock Induced Convulsions in Mice

Hossam A. El Sisi1,2, Noha A. T. Abbas1, Ibrahim A. Awwad1, and Bander A. Alrasheedi2

1Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

2College Pharmacy, Qassim University, Saudi Arabia

Received 10 July 2018; Accepted 12 February 2019

Editor: Walter Müller

Copyright © 2020 Hossam A. El Sisi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Epilepsy is a serious common neurological disease. Panax ginseng root has been identified as a potential therapy for many disorders. The present study investigated the possible anticonvulsant activity of Panax ginseng on maximal electroshock (MES) induced seizure in mice. Mice were divided into the following groups: Group A (control group): injected with normal saline then exposed to electric shock. Group B (test group): injected with sodium valproate (300 mg/kg, 600 mg/kg, 900 mg/kg). Then exposed to electric shock. Group C (test group): injected with Panax Ginseng (150, 250, 350 mg/kg) then exposed to electric shock. All animals were examined for motor coordination on rotarod test. We concluded that P. ginseng at moderate and high doses significantly decreased the HLE duration of convulsion in mice, denoting that P. ginseng has anticonvulsant effects. the antiepileptic activity of P. ginseng might be due to its antioxidative actions, anti-inflammatory, its regulating effect on sodium ion channels and/or due to its possible modulation of GABA receptor channel activity for further investigations.

Research Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 10 (2020), Article ID 101381, 4 pages
doi:10.32527/2020/101381

Panax Ginseng Inhibits Maximal Electroshock Induced Convulsions in Mice

Hossam A. El Sisi1,2, Noha A. T. Abbas1, Ibrahim A. Awwad1, and Bander A. Alrasheedi2

1Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

2College Pharmacy, Qassim University, Saudi Arabia

Received 10 July 2018; Accepted 12 February 2019

Editor: Walter Müller

Copyright © 2020 Hossam A. El Sisi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite this article

Hossam A. El Sisi, Noha A. T. Abbas, Ibrahim A. Awwad, and Bander A. Alrasheedi, "Panax Ginseng Inhibits Maximal Electroshock Induced Convulsions in Mice," Egyptian Journal of Basic and Clinical Pharmacology, Vol. 10, Article ID 101381, 4 pages, 2020. doi:10.32527/2020/101381