Mechanism for ginkgolic acid(15：1)-induced MDCK cell necrosis： Mitochondria and lysosomes damages and cell cycle arrest  

作　　者：YAO Qing-Qing LIU Zhen-Hua XU Ming-Cheng HU Hai-Hong ZHOU Hui JIANG Hui-Di YU Lu-Shan ZENG Su 

机构地区：[1]Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

出　　处：《Chinese Journal of Natural Medicines》2017年第5期375-383,共9页中国天然药物（英文版）

基　　金：supported by National Natural Science Foundation of China(No.81173120);International Science&Technology Cooperation Program of China(No.2014DFE30050)

摘　　要：Ginkgolic acids(GAs), primarily found in the leaves, nuts, and testa of ginkgo biloba, have been identified with suspected allergenic, genotoxic and cytotoxic properties. However, little information is available about GAs toxicity in kidneys and the underlying mechanism has not been thoroughly elucidated so far. Instead of GAs extract, the renal cytotoxicity of GA(15 : 1), which was isolated from the testa of Ginkgo biloba, was assessed in vitro by using MDCK cells. The action of GA(15 : 1) on cell viability was evaluated by the MTT and neutral red uptake assays. Compared with the control, the cytotoxicity of GA(15 : 1) on MDCK cells displayed a time-and dose-dependent manner, suggesting the cells mitochondria and lysosomes were damaged. It was confirmed that GA(15 : 1) resulted in the loss of cells mitochondrial trans-membrane potential(ΔΨm). In propidium iodide(PI) staining analysis, GA(15 : 1) induced cell cycle arrest at the G0/G1 and G2/M phases, influencing on the DNA synthesis and cell mitosis. Characteristics of necrotic cell death were observed in MDCK cells at the experimental conditions, as a result of DNA agarose gel electrophoresis and morphological observation of MDCK cells. In conclusion, these findings might provide useful information for a better understanding of the GA(15 : 1) induced renal toxicity.Ginkgolic acids（GAs）, primarily found in the leaves, nuts, and testa of ginkgo biloba, have been identified with suspected allergenic, genotoxic and cytotoxic properties. However, little information is available about GAs toxicity in kidneys and the underlying mechanism has not been thoroughly elucidated so far. Instead of GAs extract, the renal cytotoxicity of GA（15 ： 1）, which was isolated from the testa of Ginkgo biloba, was assessed in vitro by using MDCK cells. The action of GA（15 ： 1） on cell viability was evaluated by the MTT and neutral red uptake assays. Compared with the control, the cytotoxicity of GA（15 ： 1） on MDCK cells displayed a time-and dose-dependent manner, suggesting the cells mitochondria and lysosomes were damaged. It was confirmed that GA（15 ： 1） resulted in the loss of cells mitochondrial trans-membrane potential（ΔΨm）. In propidium iodide（PI） staining analysis, GA（15 ： 1） induced cell cycle arrest at the G0/G1 and G2/M phases, influencing on the DNA synthesis and cell mitosis. Characteristics of necrotic cell death were observed in MDCK cells at the experimental conditions, as a result of DNA agarose gel electrophoresis and morphological observation of MDCK cells. In conclusion, these findings might provide useful information for a better understanding of the GA（15 ： 1） induced renal toxicity.

关 键 词：Ginkgolic acids（15：1） Cytotoxicity Mechanism Necrosis 

分 类 号：R917[医药卫生—药物分析学]