Sub-chronic toxicity of an aqueous extract of Epimedium sagittatum (Sieb. Et Zucc.) Maxim. in rats

Abstract

Epimedium sagittatum (Sieb. et Zucc.) Maxim., a traditional medicinal plant in Asia, is widely used in clinical settings but its safety in vivo is unclear. This study investigated the sub-chronic toxicity of E. sagittatum aqueous extract to rats with a 13-week daily intragastric administration of 7.5, 15, or 30 g/kg. Nine constituents of the aqueous extract were identified by ultra-performance liquid chromatography (UPLC). Organ weights, organ coefficients, serum biochemistry parameters, histopathology, and metabolomic analysis were performed. In female rats, treatment increased the liver, thymus, and adrenal gland coefficients (p < 0.05). Liver, pancreas, and adrenal gland injury were observed. The levels of six metabolites were altered by the treatment (p < 0.05). In male rats, treatment altered liver, heart, and thymus coefficients (p < 0.05) and liver, adrenal gland, and heart injury were observed. The levels of 11 metabolites were altered (p < 0.05). The no-observed-adverse-effect level was not determined but would be below 7.5 g/kg in rats treated for 13 weeks. In female rats, E. sagittatum may injure the liver and pancreas and dysregulate the biosynthesis of phenylalanine, tyrosine, tryptophan, valine, leucine, and isoleucine and the metabolism of phenylalanine. In male rats, the extract may injure the liver and adrenal gland and dysregulate the biosynthesis of valine, leucine, and isoleucine and the metabolism of pyruvate.

Keywords:

• Metabolomics
• sex difference
• GC-MS
• pyruvate
• phenylalanine
• hepatotoxicity

Disclosure statement

The authors report no conflict of interest.

Data availability statement

The data sets analyzed during this study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [grant number 81803797], Tianjin Natural Science Foundation [grant number 18JCYBJC28700], and Technology Major Projects for ‘Major New Drugs Innovation and Development’ [grant number 2015ZX09501004-003–004].