Crocin Attenuates Kindling Development and Associated Cognitive Impairments in Mice via Inhibiting Reactive Oxygen Species-Mediated NF-κB Activation

Basic Clin Pharmacol Toxicol. 2017 May;120(5):426-433. doi: 10.1111/bcpt.12694. Epub 2016 Dec 12.

Abstract

Crocin is a pharmacologically active carotenoid pigment mainly present in the stigmas of Crocus sativus L. (Iridaceae). It has been well explored in experimental animal models of cognitive impairments, depression, anxiety and epilepsy. This study was designed to understand the effect of crocin on pentylenetetrazol (PTZ)-induced kindling development and its associated cognitive deficit in mouse. Crocin treatment at 5, 10 and 20 mg/kg p.o. doses showed a marked reduction in severity of PTZ-induced seizures. There was an increase in novel object preference index and discrimination ratio in the crocin-treated groups in the novel object recognition test. Its treatment also increased percentage spontaneous alternations in T-maze test at all the tested doses. Histopathological examination by Nissl staining showed a reduction in dark neurons in the hippocampal pyramidal layer of crocin-treated animals in contrast to vehicle control, indicating a decrease in neuronal damage. Biochemical estimations showed a significant increase in superoxide dismutase activity and reduced reactive oxygen species (ROS) in the hippocampus of crocin-treated animals. Immunohistochemistry results revealed attenuation in the levels of nuclear factor-κB (NF-κB) and phosphorylated NF-κB in the hippocampal sections of crocin-treated animals. The results of this study concluded that crocin treatment increased seizure threshold, thus inhibiting PTZ-induced kindling development and improving cognitive functions. The effect was found to be due to suppression of seizure-induced ROS generation and its linked NF-κB pathway-associated neuronal damage.

MeSH terms

  • Animals
  • Carotenoids / administration & dosage
  • Carotenoids / isolation & purification
  • Carotenoids / pharmacology*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / physiopathology
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / physiopathology
  • Crocus / chemistry
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Kindling, Neurologic / drug effects
  • Male
  • Maze Learning / drug effects
  • Mice
  • NF-kappa B / metabolism
  • Neurons / pathology
  • Pentylenetetrazole
  • Reactive Oxygen Species / metabolism*
  • Seizures
  • Severity of Illness Index
  • Superoxide Dismutase / metabolism

Substances

  • NF-kappa B
  • Reactive Oxygen Species
  • Carotenoids
  • crocin
  • Superoxide Dismutase
  • Pentylenetetrazole