4.2 Article

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

Journal

DRUG AND CHEMICAL TOXICOLOGY
Volume 46, Issue 3, Pages 451-461

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/01480545.2022.2050749

Keywords

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

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This study investigated the sub-chronic toxicity of Epimedium sagittatum aqueous extract in rats. The results showed that the extract may cause liver and pancreas injury as well as dysregulation of certain metabolic processes in female rats, and liver and adrenal gland injury as well as dysregulation of metabolic processes in male rats.
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.

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