Aroma of citral repels mice and exerts antioxidant effects as a functional food

Molecular modelling suggests that citral, one of the main components of lemongrass, interacts with Kelch-like ECH-associated protein 1, which is involved in the transcription of the antioxidant enzyme haeme oxygenase (HO)-1. A citral treatment of the pheochromocytoma (PC)12D cell line, an in vitro model of neurons, up-regulated the expression of HO-1 (mRNA: 28.7 ± 22.6, protein: 3.3 ± 0.8). The inhalation of lemongrass or citral aroma by mice decreased HO-1 mRNA levels in the ventral striatum (VSt) (0.68 ± 0.14, 0.72 ± 0.18, respectively), but not in the lateral hypothalamus or ventral tegmental area, which play important roles in appetite. Dopamine levels, which positively correlated with HO-1 mRNA expression levels in PC12D, were decreased in the murine brain by the inhalation of citral (0.79 ± 0.23). This reduction was cancelled by an injection of 6-hydroxydopamine, a selective inducer of dopaminergic neuron degeneration, into the nucleus accumbens, which is involved in pleasure, in VSt. Mice displayed aversion behaviour to the odour of citral, but no changes in their body weight. However, the oral administration of citral increased HO-1 protein levels in the murine VSt (1.25 ± 0.16). Subjects completed a questionnaire on the aroma of lemongrass essential oil, which revealed that most found it to be pleasant and it did not affect their appetite. Collectively, the present results demonstrated that humans perceive the aroma of lemongrass differently from mice, indicating its utility as a vermin repellent and antioxidant food.