Protective effect of Wuling mycelia, alone and in combination with valproic acid, on pentylenetetrazolinduced epilepsy in rats

Abstract

Purpose: To determine the inhibitory effects of Wuling mycelia, alone and in combination with valproic acid (VPA) on pentylenetetrazol (PTZ)-induced epileptic seizure in rats, and their protective effects on cognitive impairment.Methods: Sprague-Dawley rats were randomly divided into five groups: control (sham), model, Wuling mycelia, VPA and combination groups. Rats in Wuling mycelia group were given oral Wuling mycelia alone at a dose of 594 mg/kg, while those in VPA group were given oral VPA alone at a dose of 189 mg/kg. In the combination group, rats received oral VPA at a dose of 189 mg/kg co-administered with Wuling mycelia at a dose of 594 mg/kg. One hour after the treatments, the control group was injected with physiological saline intraperitoneally, while the other four groups were injected with PTZ solution once a day for 28 days. Subsequently, seizure intensity, cognitive impairment, neuronal loss and hippocampal expressions of IL-1β, NF-ĸB/p65 and TLR4 were determine in all groups.Results: Combined use of Wuling mycelium and VPA significantly reduced the frequency and the grade of seizures (p <0.01), and also decreased the degree of cognitive impairment (p <0.05). There were marked increases in neuronal damage and hippocampal  expression levels of NF-ĸB/p65, TLR4 and IL1β (inflammatory cytokines) in the model group (p < 0.05). However, these changes were  reversed in the combination treatment group (p < 0.05).Conclusion: Wuling mycelia is a potentially effective adjunct drug for the treatment of refractory epilepsy. The underlying mechanism might involve downregulations of NF-ĸB/p65, TLR4 and IL-1β. Keywords: Wuling mycelia, Refractory epilepsy, Seizure, Traditional Chinese medicine, Hippocampal area, HMGB1/TLR4/NF-κB  signalling pathway, IL-1β, NF-ĸB/p65, TLR4