Protective effect of compound Danshen (Salvia miltiorrhiza) dripping pills alone and in combination with carbamazepine on kainic acid-induced temporal lobe epilepsy and cognitive impairment in rats

Pharm Biol. 2018 Dec;56(1):217-224. doi: 10.1080/13880209.2018.1432665.

Abstract

Context: Temporal lobe epilepsy (TLE) is resistant to antiepileptic drugs (AEDs) and is associated with cognitive impairment. The modern Chinese medicine, compound Danshen dripping pills (CDDP), is clinically effective in treating epilepsy and improving cognitive impairment.

Objective: This study evaluated the protective effects of CDDP alone and in combination with carbamazepine (CBZ) on kainic acid-induced TLE and cognitive impairment in rats.

Materials and methods: Sprague-Dawley rats were randomly divided into five groups: control (sham operated), model, CDDP, CBZ and combined. A TLE model was then created via bilateral intrahippocampal injection of 0.35 μg kainic acid (KA). Rats received CDDP (85 mg/kg), CBZ (100 mg/kg) or combined (85 mg/kg CDDP +100 mg/kg CBZ) via intragastric administration for 90 d, respectively. Seizure intensity, apoptosis and glial cell line-derived neurotrophic factor (GDNF) were measured. Furthermore, the improvement in cognitive impairment and hippocampal neuronal damage was evaluated.

Results: CDDP combined with CBZ significantly decreased seizure severity and frequency (p < 0.05) and ameliorated cognitive impairment (p < 0.05). The model group showed a significant reduction of neurons and Bcl-2/Bax expression in the hippocampus CA3 area (p < 0.01), the combined groups significantly reversed these change (p < 0.01). GDNF expression in the combined groups showed a clear increase over the model group (p < 0.05).

Conclusion: These findings support the use of CDDP as an adjuvant drug for the treatment of TLE and cognitive deficit. Its mechanism might be related to an anti-apoptosis effect and up-regulation of GDNF.

Keywords: Intractable epilepsy; anti-apoptosis; antiepileptic drugs; glial cell line-derived neurotrophic factor; hippocampal CA3 area; traditional Chinese medicine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Apoptosis / drug effects
  • Behavior, Animal / drug effects*
  • CA3 Region, Hippocampal / drug effects*
  • CA3 Region, Hippocampal / metabolism
  • CA3 Region, Hippocampal / pathology
  • CA3 Region, Hippocampal / physiopathology
  • Camphanes
  • Carbamazepine / pharmacology*
  • Cognition / drug effects*
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / physiopathology
  • Cognitive Dysfunction / prevention & control*
  • Cognitive Dysfunction / psychology
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Drugs, Chinese Herbal / pharmacology*
  • Epilepsy, Temporal Lobe / metabolism
  • Epilepsy, Temporal Lobe / pathology
  • Epilepsy, Temporal Lobe / physiopathology
  • Epilepsy, Temporal Lobe / prevention & control*
  • Escape Reaction / drug effects
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Kainic Acid*
  • Male
  • Maze Learning / drug effects
  • Panax notoginseng
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Salvia miltiorrhiza
  • Time Factors
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anticonvulsants
  • Bax protein, rat
  • Bcl2 protein, rat
  • Camphanes
  • Drugs, Chinese Herbal
  • Glial Cell Line-Derived Neurotrophic Factor
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • danshen dripping pill
  • Carbamazepine
  • Kainic Acid

Grants and funding

This study was supported by the National Natural Science Foundation of China [Grant no. 81550048].