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Purpose: To investigate the effect of Wuling powder (WP) on the pharmacokinetics of valproic acid (VPA) in epileptic rats. Methods: A model of epilepsy was established in SD rats by intraperitoneal injection of pentylenetetrazole (PTZ). Twelve epileptic rats were randomly divided into two groups: control group given oral VPA alone at a dose of 180 mg/kg VPA, and drug combination group orally given VPA (180 mg/kg) co-administered with WP at a dose of 200 mg/kg. Blood sample (0.5 mL) was collected at 15, 30, 60, 120, 240 and 720 min after drug administration for measurement of plasma concentrations of VPA using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results: The AUC (0-480min) and maximum plasma concentrations (Cmax) of VPA in the drug combination group were significantly higher than those in the control group (p < 0.01). The half-time (t1/2) and time taken to attain maximum plasma VPA concentration (Tmax) in the combination group were extended, when compared to control group (p < 0.05). Conclusion: These results demonstrate that WP increases the plasma concentration of VPA and affects the pharmacokinetic properties of VPA in epileptic rats. Thus, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing WP to epileptic patients already taking VPA. [ABSTRACT FROM AUTHOR]

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-ΚB/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-ΚB/p65, TLR4 and IL- 1β (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-ΚB/p65, TLR4 and IL-1β. [ABSTRACT FROM AUTHOR]