Safety of Nutmeg powder by oral exposure: Toxicity prediction and in vivo evaluation.

Nutmeg (Myristica fragrans Houtt.) is widely cultivated in tropical regions and valued for its culinary and medicinal uses. However, its safety profile remains underexplored. This study aimed to evaluate the safety of nutmeg powder through in-silico toxicity predictions, acute oral toxicity, and a 13-week repeated-dose toxicity assessment. In the in-silico study, bioactive compounds identified via High-Performance Liquid Chromatography (HPLC) were analyzed for toxicity parameters using the ProTox II server. For acute toxicity, a single dose of nutmeg powder was administered to mice, with no mortality observed over 14 days, and an LD50 greater than 5000 mg/kg body weight was determined. In the sub-chronic toxicity study, rats received nutmeg powder at 1400 mg/kg and 3500 mg/kg (35 and 87.5 times the human therapeutic dosage, respectively) for 90 days. A 28-day recovery phase was included to assess delayed or reversible effects. The results indicate that a dose of 1400 mg/kg leads to liver damage and hemosiderin deposition in the spleen, while a dose of 3500 mg/kg causes liver and kidney damage, as well as hemosiderin deposition in the spleen. These findings highlight the potential toxicity of long-term nutmeg consumption and underscore the need for further research to ensure its safety in preclinical.