Mechanisms and Safety of Antidepressant-Like Effect of Nutmeg in Mice

• Published in: Biological & pharmaceutical bulletin Vol. 45; no. 6; pp. 738 - 742
• Main Authors: Iwata, Naohiro, Kobayashi, Daisuke, Kawashiri, Takehiro, Kubota, Toshio, Kawano, Kotomi, Yamamuro, Yuki, Miyagi, Anna, Deguchi, Yuya, Chijimatsu, Takeshi, Shimazoe, Takao
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01-06-2022; Japan Science and Technology Agency
• Subjects: Acute toxicity; acute toxicity test; Ames test; antidepressant; Antidepressants; central nervous system; Herbal medicine; Ketanserin; Locomotor activity; n-Hexane; Norepinephrine; nutmeg n-hexane extract; Serotonin S1 receptors; Serotonin S3 receptors; tail suspension test; Yohimbine; tail suspension test; nutmeg n-hexane extract; Ames test; antidepressant; acute toxicity test; central nervous system
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b21-01059

Nutmeg, a dried seed kernel of a tall evergreen Myristicaceae tree, is widely used as a spice and herbal medicine and is known to have antidepressant-like effects. This study evaluates the mechanisms underlying this antidepressant-like effect and safety of nutmeg n-hexane extract (NNE) in mice. Tail suspension and open field tests showed that NNE (10 mg/kg, per OS (p.o.)) significantly decreased the immobility time of mice without effecting their spontaneous locomotor activity. The reduction of immobility time of mice elicited by NNE was significantly inhibited by ketanserin (5-hydroxytryptamine (5-HT)2A/2C receptor antagonist), ondansetron (5-HT3 receptor antagonist), and yohimbine (α2 receptor antagonist). WAY100635 (5-HT1A receptor antagonist) tended to inhibit the effect of NNE but without significance. Testing according to the Organisation for Economic Co-operation and Development Guidelines, no mice died due to administrated NNE (2000 mg/kg, p.o.), and behavioral and weight changes were not seen in the acute toxicity test. In the Ames test, no increase in the number of revertant colonies for each bacterial strain test strains TA98 and TA100 by nutmeg powder was observed either with or without metabolic activity by S9 mix. These results suggest that NNE shows an antidepressant-like effect involving various serotonergic and noradrenergic nervous systems and maybe a highly safe natural preparation.