UPLC-HDMS-based on serum metabolomics reveals the toxicity of arecae semen

Arecae semen has been used as vermifuge and digestant in traditional Chinese medicine (TCM) for more than one thousand years. However, the toxicity effect of areca semen and its underlying mechanism are still unclear.This study was aimed to investigate the toxicity of arecae semen and to explore its mechanisms by serum metabolomics.The male Wistar rats were divided into the control group and treated group (n = 6 in each group), which were given by gavage with distill water or arecae semen aqueous extract (ASAE) once a day for 30 days, respectively. Serum samples were collected from all the rats after treatment of 7-day, 14-day and 30-day for metabolomics analysis. Moreover, biochemistry analysis and histopathological examination were performed at the end of study.The phenomenon of diarrhea, less physical activity, tremors and body curl up were observed in the treated group. Additionally, the body weights of treated rats were significantly decreased compared with control rats from the 8th day after oral administration. Except the level of creatinekinase (CK) in the treated group significantly increased compared with the control group, there were no differences on biochemistry parameters and histopathological test in the two groups. Combined with the methods of principal component analysis (PCA), orthogonal projection to latent structure-discrimination analysis (OPLS-DA) and available databases, the treated and control rats were clearly distinguished from each other and 19 metabolites were identified as the potential biomarkers in the arecae semen treated rats. The identified biomarkers indicated that there were perturbations of the phospholipid metabolism, amino acid metabolism and fat acid metabolism in the treated group.This indicated that arecae semen possessed certain cardiotoxicity and inhibited the normal growth in Wistar male rats. In addition, the metabolomics approach is a useful tool to study the toxicity in TCM.