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Pharm Biol. 2016 Jul;54(7):1209-18. doi: 10.3109/13880209.2015.1063673. Epub 2015 Jul 8.

Protective effect on phenytoin-induced cognition deficit in pentylenetetrazol kindled mice: A repertoire of Glycyrrhiza glabra flavonoid antioxidants.

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a Department of Pharmacology , Chitkara College of Pharmacy, Chitkara University , Patiala , Punjab , India and.
b Department of Pharmaceutical Sciences and Drug Research , Punjabi University , Patiala , Punjab , India.



Glycyrrhiza glabra L. (Febaceae) has been widely used in traditional medicine and scientifically explored for its anticonvulsant and memory improving potential.


The objective of this study is to investigate the effect of flavonoid rich fraction of G. glabra root extract against phenytoin-induced cognition deficit in pentylenetetrazol (PTZ) kindled mice.


The ethyl acetate fraction was initially screened in different in vitro free radical scavenging assays. For in vivo studies, the kindled mice in different groups were given 15 d post-treatment with phenytoin (25 mg/kg; p.o.) per se or in combination with varying doses of the fraction (5, 10, and 15 mg/kg; p.o.). Seizure severity score and cognitive functions were accessed using Racine's scale and passive shock avoidance paradigm, respectively on every 5th d after a PTZ challenge dose (35 mg/kg; i.p.). At the end of study, the animals were scarified for cerebral biochemistry.


The fraction showed marked antioxidant activity indicated by low IC50 values in DPPH (20.9 µg/mL), nitric oxide radical scavenging (195.2 µg/mL), and capacity of hydrogen peroxide scavenging (3.4 µg/mL) assays. Treatment with phenytoin per se and along with the flavonoid rich fraction showed significant reduction in seizure severity score as compared to vehicle control. The combined-treated groups also showed improved cognitive functions indicated by reduced number of mistakes and increased step-down latency in passive shock avoidance paradigm.


From the results, it can be concluded that the flavonoid rich fraction in combination with phenytoin reduces seizure severity and improve cognitive functions in PTZ-kindled mice.


Epilepsy; epileptic comorbidities; flavonoid-rich fraction; glutathione; nitric oxide

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