Safety assessment of melinjo (Gnetum gnemon L.) seed extract: acute and subchronic toxicity studies

Melinjo (Gnetum gnemon L.) is widely cultivated in Southeast Asia. Its fruit and seeds are common ingredients in Indonesian foods. The seeds are very rich in resveratrol dimers such as gnetin C and its glucosides, gnemonoside A and gnemonoside D, and also contain trans-resveratrol and its glucoside, trans-piceid. The safety of melinjo seeds is assured, since people in Southeast Asia have consumed them for a long time; however, their safety has not been scientifically verified. In this study, the safety of melinjo seed extract (MSE) powder was assessed in an acute oral toxicity study, a 4-week repeated dose toxicity study, and in a micronucleus test in rats. In the acute and subchronic toxicity studies, the group administered the powder did not show any toxicologically significant MSE-related changes, compared with the control group. The no observed adverse effect level (NOAEL) was determined as 1000 mg/kg/day. A genotoxicity test (rat bone marrow micronucleus test) was negative for MSE powder at levels up to 4000 mg/kg/day. These results might provide supportive evidence of safety of melinjo seeds, which has been used as food ingredients for a long time.