Journal of Natural Medicines

, Volume 71, Issue 1, pp 181–189 | Cite as

Nobiletin improves emotional and novelty recognition memory but not spatial referential memory

  • Jiyun Kang
  • Jung-Won Shin
  • Yoo-rim Kim
  • Kelley M. Swanberg
  • Yooseung Kim
  • Jae Ryong Bae
  • Young Ki Kim
  • Jinwon Lee
  • Soo-yeon Kim
  • Nak-Won Sohn
  • Sungho Maeng
Original Paper


How to maintain and enhance cognitive functions for both aged and young populations is a highly interesting subject. But candidate memory-enhancing reagents are tested almost exclusively on lesioned or aged animals. Also, there is insufficient information on the type of memory these reagents can improve. Working memory, located in the prefrontal cortex, manages short-term sensory information, but, by gaining significant relevance, this information is converted to long-term memory by hippocampal formation and/or amygdala, followed by tagging with space–time or emotional cues, respectively. Nobiletin is a product of citrus peel known for cognitive-enhancing effects in various pharmacological and neurodegenerative disease models, yet, it is not well studied in non-lesioned animals and the type of memory that nobiletin can improve remains unclear. In this study, 8-week-old male mice were tested using behavioral measurements for working, spatial referential, emotional and visual recognition memory after daily administration of nobiletin. While nobiletin did not induce any change of spontaneous activity in the open field test, freezing by fear conditioning and novel object recognition increased. However, the effectiveness of spatial navigation in the Y-maze and Morris water maze was not improved. These results mean that nobiletin can specifically improve memories of emotionally salient information associated with fear and novelty, but not of spatial information without emotional saliency. Accordingly, the use of nobiletin on normal subjects as a memory enhancer would be more effective on emotional types but may have limited value for the improvement of episodic memories.


Nobiletin Donepezil Working memory Contextual memory Emotional memory Visual recognition memory 



Protein kinase A


Extracellular signal-regulated kinase


Cyclic-AMP-responsive-element-binding protein


Long-term potentiation


Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid





Analysis of variation

Tukey’s HSD

Tukey’s honest significant difference


Standard error of the mean



The authors have no conflicts of interest to disclose. Financial support and preparation of the article was provided by the corresponding author. The research was conduct mainly by the first two authors. Other co-authors contributed to study design, data analysis and interpretation. No funding sources were involved.


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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2016

Authors and Affiliations

  • Jiyun Kang
    • 1
  • Jung-Won Shin
    • 1
  • Yoo-rim Kim
    • 1
  • Kelley M. Swanberg
    • 1
  • Yooseung Kim
    • 2
  • Jae Ryong Bae
    • 1
  • Young Ki Kim
    • 1
  • Jinwon Lee
    • 1
  • Soo-yeon Kim
    • 1
  • Nak-Won Sohn
    • 1
  • Sungho Maeng
    • 1
    • 3
  1. 1.Graduate School of East-West Medical ScienceKyung Hee UniversityYonginRepublic of Korea
  2. 2.Department of Clinical Korean Medicine Graduate SchoolKyung Hee UniversitySeoulRepublic of Korea
  3. 3.East-West Medical Research InstituteKyung Hee UniversitySeoulRepublic of Korea

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