, Volume 64, Issue 21, pp 2848-2857

Hepatic effects of Cimicifuga racemosa extract in vivo and in vitro

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Abstract.

Extracts of Cimicifuga racemosa are used frequently for menopausal complaints. Cimicifuga is well tolerated but can occasionally cause liver injury. To assess hepatotoxicity of cimicifuga in more detail, ethanolic C. racemosa extract was administered orally to rats, and liver sections were analyzed by electron microscopy. Tests for cytotoxicity, mitochondrial toxicity and apoptosis/necrosis were performed using HepG2 cells. Mitochondrial toxicity was studied using isolated rat liver mitochondria. Microvesicular steatosis was found in rats treated with > 500 μg/kg body weight cimicifuga extract. In vitro, cytotoxicity was apparent at concentrations ≥ 75 μg/mL, and mitochondrial β-oxidation was impaired at concentrations ≥ 10 μg/mL. The mitochondrial membrane potential was decreased at concentrations ≥ 100 μg/mL, and oxidative phosphorylation was impaired at concentrations ≥ 300 μg/mL. The mechanism of cell death was predominantly apoptosis. C. racemosa exerts toxicity in vivo and in vitro, eventually resulting in apoptotic cell death. The results are compatible with idiosyncratic hepatotoxicity as observed in patients treated with cimicifuga extracts.

Received 13 August 2007; received after revision 15 September 2007; accepted 25 September 2007
S. Lüde, M. Török: These authors contributed equally to this work.
An erratum to this article can be found online at http://dx.doi.org/10.1007/s00018-010-0310-1.