Effect of Rongchang capsule (茸菖胶囊) on seizure behavior,cognitive impairment,and hippocampal DNA damage and inflammatory factors in epileptic rats

OBJECTIVE: To observe the behavioral changes and changes in DNA fragments and related inflammatory factors in the hippocampus of epileptic rats pretreated with Rongchang capsule(茸菖胶囊).METHODS: Eighty Sprague-Dawley rats were randomly divided into the normal group(NG), model group(MG), sodium valproate group(VG), and Rongchang capsule group(RG)(n = 20 in each group). Pentylentetrazol was administered to the MG, VG, and RG to induce epilepsy. The VG and RG were pretreated with 1/2 the therapeutic dose of sodium valproate and Rongchang capsule, respectively. Changes in convulsion behavior and water maze learning were observed. Single cell gel electrophoresis was used to detect changes in the DNA in the hippocampus. The tail length(TL) and Olive tail moment(OTM) of cells were analyzed by GASP software. The expression of interleukin-1β(IL-1β),high mobility group box 1(HMGB1), transforming growth factor-β(TGF-β), and CCL4 in the hippocampus was determined by Western blotting.RESULTS: Rongchang capsule had a weaker effect on convulsive latency than sodium valproate, but significantly reduced seizure susceptibility. The spatial learning ability of the RG was better than that of the VG(P ≤ 0.01). The TL and OTM were significantly higher in the MG than the NG(P < 0.01). The RG had a better TL and OTM than the VG(P < 0.01).Combined with the microscopy results, DNA damage was most pronounced in the MG. Drug intervention decreased the DNA damage in the VG and RG. The expressions of IL-1β, CCL4, and HMGB1 in the hippocampus were significantly greater in the MG than the NG(P < 0.01), and were significantly reduced in the RG and VG compared with the MG(P < 0.01);however, there was no intergroup difference in the expression of TGF-β. The average values for the expression of inflammatory factors in the hippocampus were higher in the RG than in the VG;thus, Rongchang capsule may have a weaker effect on reducing the expression of inflammatory factors in the hippocampus than sodium valproate.CONCLUSION: Pretreatment with Rongchang capsule prevents or delays cognitive impairment in rats with induced epilepsy, reduces hippocampal DNA damage, and decreases the hippocampal expressions of IL-1β, CCL4, and HMGB1.

Rongchang and Xifeng capsules suppress pentylenetetrazole-induced seizures and change rest/wake behavior in zebrafish larvae

OBJECTIVE:To evaluate the effects of Rongchang capsule and Xifeng capsule on pentylenetetrazoleinduced epilepsy in zebrafish larvae and to explore the possible mechanisms behind their actions.METHODS:We utilized a trajectory tracking system to monitor seizures in zebrafish larva to confirm that certain concentrations of Rongchang capsule and Xifeng capsule produce antiepileptic effects.c-fos expression was assessed by quantitative reverse transcription-polymerase chain reaction to validate the efficacy of the capsules.Rest/wake behavior and correlation analysis predicted the targets of Rongchang capsule and Xifeng capsule.RESULTS:Larval movement times and total distances traveled by zebrafish larvae experiencing pentylenetetrazole(PTZ)-induced seizures were decreasedbyvalproatetreatment.Rongchang(500μg/m L)and Xifeng(200μg/m L)rescued the epileptic behaviors and down-regulated c-fos expression in the brains of larvae,which indicated antiepileptic effects.The rest/wake behavioral profiles showed that Rongchang and Xifeng differentially decreased rest time at night and increased larval locomotor activities during the day.Based on correlation between the actions of the two capsules and known compounds,we predicted that they might change rest/wake behaviors by affecting serotonin,GABAergic and histamine signaling pathways.CONCLUSION:The efficacy of Rongchang capsule and Xifeng capsule in alleviating epilepsy-like behaviors and molecular responses was confirmed.Our study provides insight into the capsules'effect on epilepsy.