Appetite-enhancing effects of nutmeg oil and structure-activity relationship of habituation to phenylpropanoids

Nutmeg (Myristica fragrans) is widely used to flavour sweet and savoury foods and has been used as a herbal medicine to enhance appetite in Asian countries. Nutmeg oil contains compounds such as myristicin and methyl eugenol. Previously, we found that inhalation of phenylpropanoid compounds increased appetite in mice. These volatile aroma compounds with appetite-enhancing effects have attracted the attention of healthcare professionals who care for older people with dementia because many of these older people have hypophagia, which leads to frailty and becoming bedridden. Thus, appetite-enhancing agents that are inexpensive and easy to administer are particularly desirable. In this study, we showed that the inhalation of nutmeg oil, myristicin and methyl eugenol produced appetite-enhancing effects in mice. Methyl eugenol alone has shown appetite-enhancing effects and locomotor-reducing effects at the same dose. In a previous study, benzylacetone produced those two effects at the same dose and also increased the body weight of mice significantly; methyl eugenol, however, did not because the mice experienced olfactory habituation after repeated inhalations of methyl eugenol. A structure-activity study showed that a carbonyl group on the aliphatic chain prevented habituation to aroma compounds, which is important information for identifying suitable phenylpropanoid compounds for long-term treatment of loss of appetite.