The New York Botanical Garden, Bronx, NY, 10458, USA; Lehman College and the Graduate Center, City University of New York, New York, NY, USA; Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA.
National Institute for the Study and Control of Tumors and Environmental Diseases "B. Ramazzini", Bologna, Italy; European Foundation for Research on Cancer, Environmental and Occupational Medicine "Ruberti-Schileo", Italy.
Food Chem Toxicol. 2018 Oct;120:356-366. doi: 10.1016/j.fct.2018.06.064. Epub 2018 Jun 30.
Previous studies indicate that the herb black cohosh (Actaea racemosa L.) and the triterpene glycoside actein inhibit the growth of human breast cancer cells and activate stress-associated responses. This study assessed the transcriptomic effects of black cohosh and actein on rat liver tissue, using Ingenuity and ToxFX analyses. Sprague-Dawley rats were treated with an extract of black cohosh enriched in triterpene glycosides (27%) for 24 h or actein for 6 and 24 h, at 35.7 mg/kg, and liver tissue collected for gene expression analysis. Ingenuity analysis indicates the top canonical pathways are, for black cohosh, RAR Activation, and, for actein, Superpathway of Cholesterol Biosynthesis, at 24 h. Actein alters the expression of cholesterol biosynthetic genes, but does not inhibit HMG-CoA reductase activity. Black cohosh and actein inhibited the growth of human breast and colon cancer cells and synergized with the statin simvastatin. Combinations of black cohosh with certain classes of statins could enhance their activity, as well as toxic, such as inflammatory liver, side effects. Transcriptomic analysis indicates black cohosh and actein warrant further study to prevent and treat cancer and lipid disorders. This study lays the basis for an approach to characterize the mode of action and toxicity of herbal medicines.
先前的研究表明，草药黑升麻（Actaea racemosa L.）和三萜糖苷类化合物阿克替因可抑制人乳腺癌细胞的生长并激活与应激相关的反应。本研究使用Ingenuity 和 ToxFX 分析评估了黑升麻和阿克替因对大鼠肝组织的转录组效应。Sprague-Dawley 大鼠用富含三萜糖苷（27%）的黑升麻提取物处理 24 小时，或用阿克替因处理 6 和 24 小时，剂量为 35.7mg/kg，并收集肝组织进行基因表达分析。Ingenuity 分析表明，黑升麻的主要经典途径是 RAR 激活，阿克替因的是胆固醇生物合成的超途径，时间均为 24 小时。阿克替因改变了胆固醇生物合成基因的表达，但不抑制 HMG-CoA 还原酶的活性。黑升麻和阿克替因抑制了人乳腺癌和结肠癌细胞的生长，并与他汀类药物辛伐他汀协同作用。黑升麻与某些类别的他汀类药物的组合可以增强它们的活性，同时也会增加毒性，如炎症性肝损伤等副作用。转录组分析表明，黑升麻和阿克替因值得进一步研究，以预防和治疗癌症和脂质代谢紊乱。本研究为研究草药的作用模式和毒性奠定了基础。
