Antidepressant-like Effect of Citrus sinensis (L.) Osbeck Essential Oil and Its Main Component Limonene on Mice

J Agric Food Chem. 2019 Dec 18;67(50):13817-13828. doi: 10.1021/acs.jafc.9b00650. Epub 2019 Apr 2.


The present study investigated the antidepressant-like effects of navel orange [Citrus sinensis (L.) Osbeck] essential oil (OEO) and its main components using the chronic unpredictable mild stress (CUMS) model mice and explored its possible mechanisms. The results indicated that OEO inhalation significantly ameliorated the depression-like behaviors of CUMS mice with decreased body weight, sucrose preference, curiosity, and mobility as well as shortened immobile time and attenuated dyslipidemia. Limonene was the most abundant compound in the sniffing OEO environment and mice brain after sniffing, and it was not metabolized immediately in the brain. In addition, limonene inhalation significantly restored CUMS-induced depressive behavior, hyperactivity of hypothalamic-pituitary-adrenal axis, and the decrease of monoamine neurotransmitter levels, with downregulation of brain-derived neurotrophic factor and its receptor expression in the hippocampus. Thus, the study indicates that the improvements in neuroendocrine, neurotrophic, and monoaminergic systems are related to the antidepressant effects of limonene.

Keywords: antidepressive mechanism; chronic unpredictable mild stress model; essential oil from navel orange; limonene; olfactory pathway.

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / chemistry
  • Brain-Derived Neurotrophic Factor / metabolism
  • Citrus sinensis / chemistry*
  • Depression / drug therapy*
  • Depression / metabolism
  • Depression / psychology
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Limonene / administration & dosage*
  • Limonene / chemistry
  • Male
  • Mice
  • Oils, Volatile / administration & dosage*
  • Oils, Volatile / chemistry


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Oils, Volatile
  • Limonene