Hepatic effects of Cimicifuga racemosa extract in vivo and in vitro

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 > 1,000 mg/kg [DOSAGE ERROR CORRECTED] body weight cimicifuga extract. In vitro, cytotoxicity was apparent at concentrations > or =75 microg/mL, and mitochondrial beta-oxidation was impaired at concentrations > or =10 microg/mL. The mitochondrial membrane potential was decreased at concentrations > or =100 microg/mL, and oxidative phosphorylation was impaired at concenq trations > or =300 microg/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.

Influence of black cohosh (Cimicifuga racemosa) use by postmenopausal women on total hepatic perfusion and liver functions

“…Such findings are in agreement with those of two recent studies (9,20). However, our findings do not agree with those of a recent animal study stating that C. racemosa exerted hepatotoxicity in vivo and in vitro, eventually resulting in apoptotic cell death in rats (21).…”

Cimicifuga racemosa impairs fatty acid β-oxidation and induces oxidative stress in livers of ovariectomized rats with renovascular hypertension

“…Therefore, in agreement with the rationale of Lüde et al [14], we considered an evaluation of the hepatotoxicity of C. racemosa in an animal model of estrogen deficiency associated with renovascular hypertension to be necessary. Estrogen deficiency is associated with a higher incidence of hepatic steatosis [15] and both are associated with oxidative stress [4,16].…”

“…Following this rationale and considering the findings of Lüde et al [14], which demonstrated that C. racemosa inhibited mitochondrial b-oxidation and induced steatosis when used at toxic concentrations, we investigated whether the effects of C. racemosa on mitochondrial and peroxisomal b-oxidation were manifested at therapeutic doses in this animal model. Interestingly, different mechanisms appeared to be involved in the b-oxidation responses in the organelles obtained from ovariectomy, hypertension induction, and C. racemosa treatment.…”

“…This study revealed that female Wistar rats treated with daily, high doses of C. racemosa (1000 mg/kg) developed microvesicular steatosis, probably as a result of an inhibition of mitochondrial fatty acid b-oxidation, demonstrated by in vitro experiments. The authors concluded that microvesicular steatosis of these animals, which had been observed only with toxic concentrations of C. racemosa, should not be considered clinically relevant for most patients but may become important for patients with underlying risk factors [14].…”

“…Lüde et al [14] performed a Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/freeradbiomed well-conducted study of the hepatotoxic potential of C. racemosa that involved in vivo and in vitro experiments. This study revealed that female Wistar rats treated with daily, high doses of C. racemosa (1000 mg/kg) developed microvesicular steatosis, probably as a result of an inhibition of mitochondrial fatty acid b-oxidation, demonstrated by in vitro experiments.…”