The purpose of this study was to assess in rats the pharmacological parameters and effects on gene expression in the liver of the
triterpene glycoside actein.
Actein, an active component from the herb black cohosh, has been shown to inhibit the proliferation of human
breast cancer cells. To conduct our assessment, we determined the molecular effects of
actein on livers from Sprague-Dawley rats treated with
actein at 35.7 mg/kg for 6 and 24 h. Chemogenomic analyses indicated that
actein elicited stress and
statin-associated responses in the liver;
actein altered expression of
cholesterol and
fatty acid biosynthetic genes, p53 pathway genes, CCND1 and ID3. Real-time RT-PCR validated that
actein induced three time-dependent patterns of gene expression in the liver: (i) a decrease followed by a significant increase of HMGCS1, HMGCR, HSD17B7, NQO1, S100A9; (ii) a progressive increase of BZRP and CYP7A1 and (iii) a significant increase followed by a decrease of CCND1 and ID3. Consistent with
actein's
statin- and stress-associated responses,
actein reduced
free fatty acid and
cholesterol content in the liver by 0.6-fold at 24 h and inhibited the growth of human HepG2
liver cancer cells. To determine the bioavailability of
actein, we collected serum samples for pharmacokinetic analysis at various times up to 24 h. The serum level of
actein peaked at 2.4 microg/mL at 6 h.
Actein's ability to alter pathways involved in
lipid disorders and
carcinogenesis may make it a new agent for preventing and treating these major disorders.