Effect of Rongchang capsule on seizure behavior, cognitive impairment, and hippocampal DNA damage and inflammatory factors in epileptic rat

J Tradit Chin Med. 2021 Jun;41(3):438-446. doi: 10.19852/j.cnki.jtcm.2021.03.012.

Abstract

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 ().

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.

Keywords: Cognitive dysfunction; Epilepsy; HMGB protein; Hippocampu; Inflammation; Interleukin-1beta; Rongchang capsule; Transforming growth factor beta.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / genetics
  • DNA Damage
  • Drugs, Chinese Herbal / pharmacology*
  • Epilepsy* / drug therapy
  • Epilepsy* / genetics
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / drug therapy*

Substances

  • Drugs, Chinese Herbal
  • Interleukin-1beta