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

• Published in: Pharmaceutical biology 2016-07, Vol.54 (7), p.1209-1218
• Main Authors: Singh, Paramdeep, Singh, Damanpreet, Goel, Rajesh K.
• Format: Article
• Language: English
• Subjects: 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; Epilepsy; epileptic comorbidities; flavonoid-rich fraction; Flavonoids - isolation & purification; Flavonoids - pharmacology; glutathione; Glycyrrhiza - chemistry; Kindling, Neurologic; Lipid Peroxidation - drug effects; Male; Memory - drug effects; Mice; nitric oxide; 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
• ISSN: 1388-0209; 1744-5116
• DOI: 10.3109/13880209.2015.1063673

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 IC 50 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.