Traditional Chinese medicinal formula Si-Wu-Tang prevents oxidative damage by activating Nrf2-mediated detoxifying/antioxidant genes

Cell & Bioscience

Ying Huang¹  Bradley Andresen¹  Sunil Prabhu¹  Arvind Thakkar¹  Moses SS Chow¹  Zhong Zuo²  Zhijun Wang¹  Ranadheer Ravula¹  Mandy Liu¹ 

[1] Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California;School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

关键词: HMOX1;    SLC7A11;    Breast cancer;    Nrf2;    ROS;    Z-liguistilide;    Si-Wu-Tang;    Cancer chemoprevention;   

Others  :  791276
DOI  :  10.1186/2045-3701-4-8

 received in 2013-09-20, accepted in 2013-11-19,  发布年份 2014

【 摘 要 】

Background

Induction of Nrf2-mediated detoxifying/antioxidant genes has been recognized as an effective strategy for cancer chemoprevention. Si-Wu-Tang (SWT), comprising the combination of four herbs, Paeoniae, Angelicae, Chuanxiong and Rehmanniae, is one of the most popular traditional oriental medicines for women’s diseases. The purpose of this study is to determine the effects of SWT on Nrf2 pathway in vitro and in vivo and to identify the active component(s).

Results

Cell viability and apoptosis were analyzed in the non-cancerous breast epithelial cell line MCF-10A after H₂O₂ treatment in the presence or absence of SWT using the Sulphorhodamine B assay, Annexin-V/Propidium iodide staining and flow cytometry. SWT strongly reduced H₂O₂ -induced cytotoxicity and apoptosis in MCF-10A cells. Expression of Nrf2 and Nrf2-regulated genes HMOX1 (heme oxygenase 1) and SLC7A11 (xCT) was evaluated by quantitative RT-PCR, Western Blot and immunocytochemistry. SWT strongly induced Nrf2-regulated genes at mRNA and protein levels and increased the nuclear translocation of Nrf2 in MCF-10A cells. The in vivo pharmacodynamic effect of SWT was evaluated in healthy female Sprague–Dawley rats. Short-term oral administration of SWT (1,000 mg/kg per day for six consecutive days) to rats resulted in an increased expression of Nrf2-regulated genes Hmox1 and Slc7A11 in the liver detected by quantitative RT-PCR. Among nine compounds that have been identified previously in the SWT products, z-liguistilide was discovered as the main component responsible for the effect of Nrf2 activation using the antioxidant response element-luciferase reporter gene assay. Z-liguistilide was confirmed with a high potency to induce Nrf2-regulated genes and Nrf2 nuclear translocation.

Conclusions

Our results demonstrated that SWT and its component z-liguistilide are able to activate the Nrf2 pathway in non-cancerous cells and organs in vitro and in vivo, suggesting that SWT might be an orally effective and nontoxic agent for cancer chemoprevention.

【 授权许可】

   
2014 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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