Safety assessment and oxidative stress evaluation of myricetin derivative-rich fraction from Syzygium malaccense in C57BL/6J mice

Myricetin derivatives from Syzygium malaccense leaf extract are known to have numerous therapeutic efficacies but there is no documented evidence corroborating its safety. Therefore, the present work aimed to evaluate the safety profile of myricetin derivative-rich fraction (MD) from S. malaccense leaf extract through single and repetitive oral administration in C57BL/6J mice. In the acute toxicity study, mice were orally administered with MD at single doses of 25, 150, 500, and 1,500 mg/kg. Subsequently, a modified sub-chronic toxicity assessment was performed by administering 150 mg/kg MD orally for 16 weeks. In both acute and sub-chronic toxicity studies, there were no lethal effects and behavioural signs of toxicity observed. The body weight, food, and water intakes of mice were normal throughout the respective experimental periods. As compared to the respective control groups, MD caused a significant improvement in serum uric acid and aspartate aminotransferase levels. The histopathological analysis of MD-administered mice did not show any inflammation or cell death. The MD-treated mice showed significantly reduced protein carbonyl and lipid hydroperoxide levels in urine, liver, and kidney tissues. Taken together, the no-observed-adverse-effect level of MD was up to 1,500 mg/kg, and considered safe for oral consumption over relatively long durations with oxidative stress attenuating properties.