title: Processing of kansui roots stir-baked with vinegar reduces kansui-induced hepatocyte cytotoxicity by decreasing the contents of toxic terpenoids and regulating the cell apoptosis pathway.
abstract: Euphorbia kansui is a Traditional Chinese Medicine widely used for the treatment of oedema, ascites and asthma. However, its serious hepatotoxicity hinders its safe clinical application. The process of stir-baking with vinegar is regularly used to reduce the toxicity of kansui. Up till now, the exact mechanism of the reduction in hepatotoxicity of kansui stir-baked with vinegar has been poorly defined. In this study, decreased  contents of five diterpene and one triterpene in kansui (GS-1) after stir-baking with vinegar (GS-2) was investigated by UPLC-QTOF/MS. Flow cytometry and Hoechst staining were used to show that the stir-baking with vinegar process reduces kansui-induced cell apoptosis. Furthermore, the result also indicated that kansui stir-baked with vinegar protects LO2 cells from apoptosis by increasing the cell mitochondrial membrane potential (ΔΨm), decreasing the release of cytochrome c and inhibiting the activities of caspase-9 and caspase-3 as evidenced by means of high content screening (HCS), ELISA and western blotting. These results suggested that the stir-baking vinegar could reduce the hepatotoxicity of kansui by effectively decreasing the contents of toxic terpenoids and inhibiting the intrinsic pathway of hepatocyte cell apoptosis. In conclusion, the study provided significant data for promoting safer and better clinical use of this herb.
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. yanxiaojing963@163.com.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yan
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. zhangli@njutcm.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. njuguo@njutcm.edu.cn.
authors.forename: Jianming
authors.initials: J
authors.lastname: Guo
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. raindc@163.com.
authors.forename: Yudan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. shex@njutcm.edu.cn.
authors.forename: Erxin
authors.initials: E
authors.lastname: Shang
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. yupingtang@njutcm.edu.cn.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. awding105@163.com.
authors.forename: Anwei
authors.initials: A
authors.lastname: Ding
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. dja@njutcm.edu.cn.
authors.forename: Jin-Ao
authors.initials: JA
authors.lastname: Duan
mesh_terms: D019342:Acetic Acid / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology*; D028481:Euphorbia / Q000737:chemistry*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D013729:Terpenes / Q000737:chemistry*
chemical_list: D004365:Drugs, Chinese Herbal; D013729:Terpenes; D019342:Acetic Acid