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Published on: November 25, 2014
Pharmacological mechanisms of black cohosh in Sprague-Dawley rats
Linda Saxe Einbond1, Morando Soffritti, Davide Degli Esposti
1Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. lseinbond@gmail.com
Background:
Studies 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.
Purpose:
This study examines the pharmacological mechanisms and toxicological effects in the short term of the herb black cohosh on female Sprague-Dawley rats.
Materials And Methods:
To 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 0mg/kg. Four animals for each group were sacrificed at 1, 6 and 24h after treatment; liver tissue and serum samples were obtained for gene expression and lipid analysis.
Results:
Microarray 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 24h and triglycerides at 6h in the serum, but increased the free fatty acid and triglyceride content of the treated livers at 24h.
Conclusion:
Our results suggest that black cohosh warrants further study for breast cancer prevention and therapy.
Insights
Black cohosh demonstrates antiproliferative effects by downregulating key genes and inhibiting liver cancer cell growth. Further research is recommended for its potential in breast cancer prevention and therapy.
Area of Science:
- Pharmacology
- Molecular Biology
- Toxicology
Background:
- Black cohosh extracts show potential in inhibiting human breast cancer cell growth.
- Molecular targets and signaling pathways remain undefined.
Purpose of the Study:
- To investigate the pharmacological mechanisms of black cohosh.
- To assess the short-term toxicological effects of black cohosh in rats.
Main Methods:
- Female Sprague-Dawley rats were treated with black cohosh extract.
- Gene expression and lipid analysis were performed on liver tissue and serum samples.
- Microarray analysis identified changes in gene activity.
Main Results:
- Black cohosh downregulated mitochondrial oxidative phosphorylation genes.
- Upregulation of phospholipid biosynthesis, PI3-Kinase, and sphingosine signaling pathways observed.
- Black cohosh repressed cyclin D1 and ID3 expression, inhibiting HepG2 cell proliferation.
- Serum lipid levels were altered, with increased lipid content in treated livers.
Conclusions:
- Black cohosh exhibits antiproliferative properties.
- The herb warrants further investigation for breast cancer prevention and therapy.
