Metabolic Brain Disease

, Volume 33, Issue 6, pp 1877–1886 | Cite as

Standardized Citrus unshiu peel extract ameliorates dexamethasone-induced neurotoxicity and depressive-like behaviors in mice

  • Dong Wook Lim
  • Min Young Um
  • Taewon Han
  • Jaekwang Lee
  • Yun Tai Kim
  • Suengmok Cho
  • In-Ho Kim
  • Daeseok Han
  • Changho Lee
Original Article


Dried Citrus unshiu peel, also known as Chinpi, have been commonly used as a traditional medicine to improve for allergy, inflammation and hepatopathy. Many previously studies have reported that citrus flavonoids show neuroprotective activities. However, the antidepressant-related effects of C. unshiu peels have not been well characterized. Here, the antidepressant-like effects of standardized C. unshiu peel extract (SCP) were evaluated in in vivo and in vitro depression models induced by dexamethasone (DEX), a synthetic glucocorticoid. Male ICR mice (9-week-old) were injected the DEX (40 mg/kg) and were orally given SCP daily (30, 100, and 300 mg/kg) for 14 consecutive days. The depressive-like behaviors were determined by use of open filed test (OFT), sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST). We show that treatment with SCP significantly alleviated DEX-induced depressive-like behaviors and reduced neurotoxicity in a concentration dependent manner in SH-SY5Y cells. Additionally, repeated DEX injection markedly decreased brain derived neurotrophic factor (BDNF) level, tropomyosin receptor kinase B (TrkB), and cyclic AMP-response element-binding protein (CREB), while SCP treatment improved these levels in the cerebral cortex and hippocampus regions. Our findings suggest that SCP exhibits significant antidepressant-like effects in the DEX-induced depressive animal model, and this activity may be mediated by preventing corticosterone-induced neurotoxicity.


Citrus unshiu peel Antidepressant Dexamethasone Neurotoxicity BDNF-TrkB-CREB pathway 



This research was supported by the Main Research Program (E0164501-03) of the Korea Food Research Institute funded by the Ministry of Science and ICT.

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Research group of Functional Food Materials, Research Division of Food FunctionalityKorea Food Research Institute (KFRI)Wanju-gunRepublic of Korea

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