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

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


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

Objective: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Epilepsy; epileptic comorbidities; flavonoid-rich fraction; glutathione; nitric oxide.

MeSH terms

  • Acetates / chemistry
  • Animals
  • Anticonvulsants / isolation & purification
  • Anticonvulsants / pharmacology*
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Cognition / drug effects*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / prevention & control*
  • Cognition Disorders / psychology
  • Disease Models, Animal
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Glycyrrhiza / chemistry
  • Kindling, Neurologic*
  • Lipid Peroxidation / drug effects
  • Male
  • Memory / drug effects
  • Mice
  • Oxidative Stress / drug effects
  • Pentylenetetrazole*
  • Phenytoin*
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Roots
  • Plants, Medicinal
  • Seizures / chemically induced
  • Seizures / metabolism
  • Seizures / physiopathology
  • Seizures / prevention & control*
  • Solvents / chemistry
  • Time Factors


  • Acetates
  • Anticonvulsants
  • Antioxidants
  • Flavonoids
  • Plant Extracts
  • Solvents
  • Phenytoin
  • ethyl acetate
  • Pentylenetetrazole