Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model

J Ethnopharmacol. 2017 Jul 31;207:226-236. doi: 10.1016/j.jep.2017.06.024. Epub 2017 Jun 19.


Ethnopharmacological relevance: The Pinus densiflora leaf has been traditionally used to treat mental health disorders as a traditional Chinese medicine. Here we examined the ethnopharmacological relevance of pine needle on memory impairment caused by stress.

Aim of the study: To elucidate the possible modulatory actions of 30% ethanolic pine needle extract (PNE) on stress-induced hippocampal excitotoxicity, we adopted an acute restraint stress mouse model.

Materials and methods: Mice were orally administered with PNE (25, 50, or 100mg/kg) or ascorbic acid (100mg/kg) for 9 days, and were then subjected to restraint stress (6h/day) for 3 days (from experimental day 7-9). To evaluate spatial cognitive and memory function, the Morris water maze was performed during experimental days 5-9.

Results: Restraint stress induced the memory impairment (the prolonged escape latency and cumulative path-length, and reduced time spent in the target quadrant), and these effects were significantly prevented by PNE treatment. The levels of corticosterone and its receptor in the sera/hippocampus were increased by restraint stress, which was normalized by PNE treatment. Restraint stress elicited the hippocampal excitotoxicity, the inflammatory response and oxidative injury as demonstrated by the increased glutamate levels, altered levels of tumor necrosis factor (TNF)-α and imbalanced oxidant-antioxidant balance biomarkers. Two immunohistochemistry activities against glial fibrillary acidic protein (GFAP)-positive astrocytes and neuronal nuclei (NeuN)-positive neurons supported the finding of excitotoxicity especially in the cornu ammonis (CA)3 region of the hippocampus. Those alterations were notably attenuated by administration of PNE.

Conclusions: The above findings showed that PNE has pharmacological properties that modulate the hippocampal excitotoxicity-derived memory impairment under severe stress conditions.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Antioxidants / metabolism
  • Ascorbic Acid / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Memory Disorders / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Oxidants / metabolism
  • Pinus / chemistry*
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / psychology


  • Antioxidants
  • Oxidants
  • Plant Extracts
  • Ascorbic Acid