Arbutin attenuates cognitive impairment and inflammatory response in pentylenetetrazol-induced kindling model of epilepsy

Arbutin as a natural soluble glycosylated phenol possesses a wide range of pharmacological activities including anti-inflammatory and anti-oxidant effects. The present study was designed to evaluate the effect of arbutin supplementation on seizures behavior, memory performance, glial activation, release of inflammatory factors and neuroprotection in pentylenetetrazole-induced kindling model. Chemical kindling was induced by repetitive injections of PTZ at subconvulsive doses (36 mg/kg). Arbutin at doses of 25 or 50 mg/kg was administrated intraperitoneally (i.p.), 10 days before PTZ injection and its application was continued 1 h before each PTZ injection. High performance liquid chromatography (HPLC) analysis was performed to measure the arbutin content in hippocampus. After monitoring the behavioral signs of seizures, Morris water maze task was used to assess the spatial learning and memory of animals. Gene expression analysis was carried out to evaluate the effect of arbutin on expression of inflammatory mediators and astrocyte activation. Furthermore, immunostaining was used to assess the protein levels of astrocytes and neurons in hippocampus. The results of HPLC analysis showed that high amount of arbutin can be detected in hippocampus of arbutin + PTZ receiving animals. The seizure behavioral manifestations and memory dysfunction were reduced by arbutin in a dose-dependent manner. The mRNA levels of TNF-alpha, IL-6 and GFAP were significantly downregulated in animals treated by arbutin. Additionally, the levels of astrocytes activation and neuronal damage were attenuated in arbutin treated animals. These results suggest that arbutin attenuates glial activation, memory impairment and release of inflammatory mediators in model of chronic epilepsy.