Crocin Improves Cognitive Behavior in Rats with Alzheimer's Disease by Regulating Endoplasmic Reticulum Stress and Apoptosis

Biomed Res Int. 2019 Aug 26;2019:9454913. doi: 10.1155/2019/9454913. eCollection 2019.


Aim: To investigate the effect of crocin on the learning and memory acquisition of AD rats and its underlying mechanisms.

Methods: A total of 48 healthy male SD rats were randomly divided into control group, AD model group, resveratrol group, and crocin group, with 12 rats per group. AD model was established by injecting Aβ 25-35 to the lateral ventricle of rats, and thereafter the rats were administrated with resveratrol (40 mg/kg), crocin (40 mg/kg), or PBS daily for 14 days. Y-maze test and sucrose preference test were used to detect the learning and memory acquisition of rats. Neuronal apoptosis was detected by TUNEL staining and Western blot for apoptosis-related proteins Bax, Bcl-2, and Caspase-3. Immunofluorescence staining and Western blot tests were used to detect the expression of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) in hippocampal CA1 region (Hippo) and prefrontal cortical neurons (PFC).

Results: The learning and memory abilities of AD rats were significantly decreased, which was significantly rescued by resveratrol and crocin. The apoptotic cell number of Hippo and PFC neurons in AD model group was significantly higher than that in control group (P<0.01), while resveratrol and crocin significantly decreased the apoptotic cell number in AD group (P<0.01). Compared with the control group, the expression of Bcl2 in PFC and hippo of AD model group was significantly decreased (P<0.01), while those of Bax, Caspase3, GRP78, and CHOP were significantly increased (P<0.01). Resveratrol and crocin could significantly reverse the expression of these proteins in AD rats (P<0.05).

Conclusion: Crocin can improve the learning and memory ability of AD rats possibly by reducing endoplasmic reticulum stress and neuronal apoptosis.

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Alzheimer Disease* / physiopathology
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Behavior, Animal / drug effects*
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / pathology
  • CA1 Region, Hippocampal / physiopathology
  • Carotenoids / pharmacology*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Cognition / drug effects*
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress / drug effects*
  • Male
  • Neurons / metabolism
  • Neurons / pathology
  • Rats
  • Rats, Wistar


  • Apoptosis Regulatory Proteins
  • Carotenoids
  • crocin