文献类型：期刊文献

英文题名：Andrographolide induce human embryonic stem cell apoptosis by oxidative stress response

作者：Huang, Huarong[1,3];Cao, Huanhuan[3,4];Xing, Chun[1];Hua, Yunfen[3,5];Zhang, Ming[3,6];Jin, Lifang[2,3]

机构：[1]Hangzhou Normal Univ, Coll Life & Environm Sci, Hangzhou, Zhejiang, Peoples R China;[2]Shaoxing Univ, Coll Life Sci, Shaoxing, Zhejiang, Peoples R China;[3]Hangzhou Precis Med Res Ctr, Hangzhou, Zhejiang, Peoples R China;[4]Hangzhou Econ & Technol Dev Area Biomed Publ Plat, Hangzhou, Zhejiang, Peoples R China;[5]Zhejiang Univ Technol, Coll Pharm Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China;[6]Zhejiang Univ, Coll Life Sci, Hangzhou, Zhejiang, Peoples R China

年份：2019

卷号：15

期号：2

起止页码：209

外文期刊名：MOLECULAR & CELLULAR TOXICOLOGY

收录：SCI-EXPANDED(收录号：WOS:000463730500011)、、Scopus(收录号：2-s2.0-85063606518)、WOS

基金：This work was partially supported by the Natural Science Foundation of Zhejiang Province Grant (LY15C070005), and Initiative Design Project of Agricultural Research of Hangzhou (20162012A07). The authors are grateful to Dr. Fan Lin for polishing the article.

语种：英文

外文关键词：Andrographolide; Human embryonic stem cells; Apoptosis; Oxidative stress; Nrf2 pathway

外文摘要：Backgrounds: The anti-inflammatory effect of andrographolide is widely accepted; however, its exact role in reproductive toxicity requires further elucidation. The embryonic stem cell test (EST) is a promising system for detecting the reproductive toxicity of drugs in vitro. In this study, we applied a prediction model to our EST data after classifying andrographolide according to published criteria. The possible mechanism of andrographolide reproductive toxicity was also studied. Methods: Reproductive toxicity of andrographolide was evaluated in vitro EST model and in vivo mouse model. Human embryonic stem cells (ESCs) were cultured with different concentrations of andrographolide with or without N-acetyl-L-cysteine (NAC). Cell viability was assessed with MTT assay, and reactive oxygen species (ROS) level was measured with DCFH-DA assay. Gene and protein expression levels were measured with qRT-PCR and western-blot, respectively. Results: Results showed that andrographolide exhibited strong reproductive toxicity according to the prediction model of the EST and mouse studies. An increase in ROS levels, damage to mitochondrial membrane potential, and induction of caspase-3 were observed in the andrographolide-treated human ESCs. Scavenging of andrographolide-induced ROS by NAC blocked these activities. Western blot and qRT-PCR analysis revealed that the nuclear factor erythroid-2-related factor 2 (Nrf2) protein and its target antioxidant genes were up-regulated after andrographolide treatment at certain concentrations. Furthermore, NAC treatment significantly increased the activity of the Nrf2 signaling pathway. Conclusion: We demonstrated that andrographolide is a drug with strong reproductive toxicity, which resulted from ROS-mediated oxidative stress. In addition, the Nrf2 pathway appears to be involved in the NAC protection of human ESCs against andrographolide-induced cell apoptosis.