NMR-based metabonomic approach on the toxicological effects of a Cimicifuga triterpenoid

Cimicifugae Rhizoma, a well-known botanical dietary supplement, has been the subject of intense interest due to its potential application for alleviating menopausal symptom. Although there are clinic data that the Cimicifuga extract should have hepatotoxicity, no evidence on the main chemical components has been reported. Cimicidol-3-O-β -d-xyloside (CX) is one of the main triterpenoids of the rhizome. This work studies the toxicological effects of CX after oral administration (50 mg kg(-1) per day) over a 7-day period in female SD rats using metabonomic analyses of (1) H NMR spectra of urine, serum and liver tissue extracts. Histopathological studies of liver and analyses of blood biochemical parameter, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen and creatinine revealed that CX had no negative impacts on liver and kidney. However, the metabolic signature of (1) H NMR-based urinalysis of daily samples displayed an increment in the levels of taurine, trimethylamine-N-oxide (TMAO), betaine and acetate. Elevated serum levels of creatinine, glucose, alanine, TMAO and betaine and lower levels of lactate were observed. Metabolic profiling on aqueous soluble extracts of liver showed simultaneously increases in succinate, glycogen, choline, glycerophosphorylcholine, TMAO and betaine levels and reduction in valine, glucose and lactate levels. Nevertheless, no changes in any metabonomic level were found in lipid-soluble extracts of liver. These findings indicate that CX has a slight toxicity in liver and kidney via disturbance of the metabolisms of energy and amino acids. The present study provides a reasonable explanation for the clinical hepatotoxicity of Cimicifuga extract.