Pharmacological mechanisms of black cohosh in Sprague-Dawley rats |
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Authors: | Einbond Linda Saxe Soffritti Morando Esposti Davide Degli Wu Hsan-Au Tibaldi Eva Lauriola Michelina He Kan Park Taesik Su Tao Huggins Lesley Wang Xiaomei Roller Marc Brennan Richard |
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Institution: | Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. lseinbond@gmail.com |
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Abstract: | BackgroundStudies indicate that extracts and purified components from black cohosh inhibit the growth of human breast cancer cells, but the molecular targets and signaling pathways have not yet been defined.PurposeThis study examines the pharmacological mechanisms and toxicological effects in the short term of the herb black cohosh on female Sprague–Dawley rats.Materials and methodsTo assess effects on gene activity and lipid content, we treated female Sprague–Dawley rats with an extract of black cohosh enriched in triterpene glycosides (27%) at 35.7 or 0 mg/kg. Four animals for each group were sacrificed at 1, 6 and 24 h after treatment; liver tissue and serum samples were obtained for gene expression and lipid analysis.ResultsMicroarray analysis of rat liver tissue indicated that black cohosh markedly downregulated mitochondrial oxidative phosphorylation genes. Phospholipid biosynthesis and remodeling, PI3-Kinase and sphingosine signaling were upregulated, driven largely by an upregulation of several isoforms of phospholipase C. Hierarchical clustering indicated that black cohosh clustered with antiproliferative compounds, specifically tubulin binding vinca alkaloids and DNA alkylators. In support of this, black cohosh repressed the expression of cyclin D1 and ID3, and inhibited the proliferation of HepG2, p53 positive, liver cancer cells. Black cohosh reduced the level of free fatty acids at 6 and 24 h and triglycerides at 6 h in the serum, but increased the free fatty acid and triglyceride content of the treated livers at 24 h.ConclusionOur results suggest that black cohosh warrants further study for breast cancer prevention and therapy. |
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Keywords: | DAG diacylglycerol IP3 inositol 1 4 5-trisphosphate MTD maximum tolerated dose PIP2 phosphatidyl-4 5-biphosphate PLC phospholipase C |
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