1. Neurobehavioral and Neurological Effects of Resveratrol on Mouse Models of Epilepsy Ubedul Hoda 1,2, Nidhi B. Agarwal 2, Nouroz Sehar 1,3, Mohd. Ashif Khan 1,4, Divya Vohora 2,4, Suhel Pervez3 1Centre for Translational and Clinical Research, Faculty of Science, Jamia Hamdard, New Delhi; 2Department of Pharmacology, Jamia Hamdard- New Delhi; 3Department of Medical Elementology and Toxicology, Jamia Hamdard , New Delhi; 4Department of Pharmaceutical Medicine, Jamia Hamdard - New Delhi
INTRODUCTION
Table 2 : Effect of Resveratrol on PTZ- induced seizure
There is an urge to identify new molecules which can modulate process of epileptogenesis, since currently available drugs act symptomatically and almost 1/3rd of the patients remain refractory to the disease.
Resveratrol (3,5,4′-tri-hydroxy-trans-stilbene) is a natural non-flavonoid polyphenolic compound found in variety of dietary sources like red wine, peanuts and grapes. (shetty et al., 2011)
It has demonstrated antioxidant, chemopreventive , hypolipeademic and cardioprotective activity.
Moreover, it has been demonstrated that resveratrol has potential beneficial effects in neurological disease models of alzhiemers, parkinsons and seizures (Lu et al., 2010; Zhang et al., 2010).
Group
Dose (mg/kg)
Myoclonic Jerk (sec)
Generalised Seizure (sec)
Control
10 ml
65±1.65
84.83±2.24
Resveratrol 10
83.33±2.07
130.16±4.65 20
829.83±33.47*
±47.90# 40
±60.56$
Data are expressed as Mean ± SEM; n=6 in each group, ANOVA followed by Tukey’s test
* p < Control vs. RESV 20 mg/kg, # p < Control vs. RESV 20 mg/kg,
@ p < Control vs. RESV 40 mg/kg, $ p < Control vs. RESV 40 mg/kg.
Table 3: Effect of Resveratrol on Step-down Latency
OBJECTIVES
Group
Dose (mg/kg)
Step-down Latency (sec)
Acquisition Latency
Retention Latency
Control
10 ml
481.33±22.8
540.83±8.2
Resveratrol 10
504.2±11.64
565±8.34* 20
526.5±17.99
585.33±2.6# 40
497.33±18.22
585.67±2.6$
To evaluate effect of acute administration of Resveratrol on ICES and
PTZ – induced seizure
To assess the effect of acute administration of Resveratrol on cognition
MATERIALS AND METHODS
ANIMALS
Strain : Swiss albino mice
Weight : g
DRUGS & DOSING SCHEDULE
Acute study : days
Resveratrol : , 20 and 40 mg/kg body wt
Phenytoin : mg/kg
Pentylenetetrazole : mg/kg, i.p
CMC : % (w/v)
NEUROPHARMACOLOGICAL EVALUATION
Seizures
Increasing current electroshock test (ICES) (Bharal et al. ,2008)
Pentylenetetrazole-induced convulsions (Bharal et al. ,2013)
Cognition
Step- down latency on Passive avoidance apparatus
Transfer latency on Elevated plus maze
Statistical analysis
Data is expressed as Mean ± SEM. ANOVA followed by tukey’s and Dunnet’s test.
Data are expressed as Mean ± SEM; n=6 in each group, ANOVA followed by Dunnet’s test.
*p < 0.05 Control vs. RESV 10 mg/kg; # p < 0.01 Control vs. RESV 20 mg/kg;
$ p < 0.01 Control vs. RESV 40 mg/kg .
Table 4: Effect of Resveratrol on Transfer latency
Group
Dose (mg/kg)
Transfer Latency (sec)
Acquisition latency
Retention Latency
Control
10 ml
16.5±0.67
9.5±0.77
Resveratrol 10
16.67±0.42
9.2±0.31 20
15.67±0.67
7.5±0.43* 40
15.5±0.62
7.67±0.42#
Data are expressed as Mean ± SEM; n=6 in each group, ANOVA followed by Dunnet’s test.
* p < 0.05 Control vs. RESV 20 mg/kg; # p < 0.05 Control vs. RESV 40 mg/kg
SUMMARY AND CONCLUSIONS
RESV possesses anticonvulsant activity against electroconvulsions and chemoconvulsions.
It is devoid of cognitive impairment which is a common side effect for most of the conventional antiepileptic drugs.
To conclude RESV may be a potential anticonvulsant for all types of seizures viz. absence, partial and tonic-clonic seizures.
RESULTS
Table1: Effect of Resveratrol on ICES
Data expressed as Mean ± SEM; n=6 in each group, ANOVA followed by Tukey’s test
* p < 0.01 Control vs. RESV 10 mg/kg, # p < Control vs. RESV 20 mg/kg,
@ p < Control vs. RESV 40 mg/kg,$ p < Control vs. Phenytoin 25 mg/kg
Group
Dose (mg/kg)
Seizure Threshold Current (STC) (mA)
Control
10 ml
14.67±0.5
Resveratrol 10
18.33±0.6* 20
28±0.7# 40
Phenytoin 25
28.33±0.6 $
REFERENCES
Bharal N., Sahaya Kinshuk, Jain Seema, Mediratta Pramod K. and Sharma K.K.; Curcumin has Anticonvulsant Activity on Increasing Current Electroshock Seizures in Mice; Phytother. Res. 22, 1660–1664 (2008)
Bharal N. Agarwal, Jain Seema, Nagpal Dheeraj, Nitin Kumar Agarwal , Pramod K. Mediratta , Krishna K. Sharma; Liposomal formulation of curcumin attenuates seizures in different experimental models of epilepsy in mice; Fundamental & Clinical Pharmacology 27 (2013) 169–172.
Lu, X., Ma, L., Ruan, L., Kong, Y., Mou, H., Zhang, Z., Wang, Z., Wang, J.M., Le, Y., Resveratrol differentially modulates inflammatory responses of microglia and astrocytes. J Neuroinflammation 7, 46.
Zhang, F., Liu, J., Shi, J.S., Anti-inflammatory activities of resveratrol in the brain: role of resveratrol in microglial activation. Eur J Pharmacol 636, 1-7.
Shetty, A.K., Promise of resveratrol for easing status epilepticus and epilepsy. Pharmacol Ther 131,
Presented at International Conference on Nurturing global healthcare (2016), Amity University - Noida