Acute toxicity profiling of medicinal herb Ardisia elliptica leaf extract by conventional evaluations and proton nuclear magnetic resonance (NMR) metabolomics

Background and aim Interest in the safety of herbal medicine is growing rapidly regarding knowledge and challenges in natural products. Hence, this study aimed to reveal the toxicological profile of Ardisia elliptica, a traditional medicinal plant used in the treatment of various illnesses. Experimental procedure Acute toxicity study was performed on female and male Sprague Dawley rats with a single oral administration of 2000 mg/kg BW of 70% ethanolic A. elliptica leaf extract, using a combination of conventional investigations and 1H-NMR-based metabolomics approaches. Results Physical, hematological, biochemical, and histopathological assessments demonstrated the usual rat profile, with no mortality and delayed toxicity 14 days after administration. 1H NMR serum metabolomics depicted similar metabolites between normal and treated groups. Nevertheless, 1H NMR of urinary metabolomics revealed perturbation in carbohydrate, amino acid, and energy metabolism within 24h after extract administration, while no accumulation of toxic biomarkers in the collected biological fluids on Day 14. A minor gender-based difference revealed the influence of sex hormones and different energy expenditure on response to extract treatment. Conclusion This study suggested that 2000 mg/kg BW of 70% ethanolic A. elliptica leaf extract is considered as safe for consumption and offered a comprehensive overview of the response of physiological and metabolic aspects applicable to food and herbal product development.