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

Abstract 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.