Gu Manman, Xu Jing, Han Chunyang, Kang Youxi, Liu Tengfei, He Yanfei, Huang Yanfei, Liu Cuiyan
College of Animal Science and Technology, Anhui Agricultural University, 130 Changjiang West Road, Hefei, Anhui 230036, China.
Evid Based Complement Alternat Med. 2015;2015:796306. doi: 10.1155/2015/796306. Epub 2015 Oct 13.
Berberine, an isoquinoline alkaloid isolated from several traditional Chinese herbal medicines (TCM), exhibits a strong antimicrobial activity in the treatment of diarrhea. However, it causes human as well as animal toxicity from heavy dosage. The present study was conducted to investigate the cytotoxicity of berberine and its possible trigger mechanisms resulting in cell cycle arrest, DNA damage, ROS (reactive oxygen species) level, mitochondrial membrane potential change, and cell apoptosis in L929 murine fibroblast (L929) cells. The cells were cultured in vitro and treated with different concentrations of berberine for 24 h. The results showed that cell viability was significantly decreased in a subjected dose-dependent state; berberine concentrations were higher than 0.05 mg/mL. Berberine at a concentration above 0.1 mg/mL altered the morphology of L929 cells. Cells at G2/M phase were clear that the level of ROS and cell apoptosis rates increased in 0.1 mg/mL group. Each DNA damage indicator score (DIS) increased in groups where concentration of berberine was above 0.025 mg/mL. The mitochondrial membrane potential counteractive balance mechanics were significantly altered when concentrations of berberine were above 0.005 mg/mL. In all, the present study suggested that berberine at high dosage exhibited cytotoxicity on L929 which was related to resultant: cell cycle arrest; DNA damage; accumulation of intracellular ROS; reduction of mitochondrial membrane potential; and cell apoptosis.
黄连素是从几种传统中药中分离出来的异喹啉生物碱，在治疗腹泻方面具有很强的抗菌活性。然而，高剂量使用会导致人和动物中毒。本研究旨在探讨黄连素对L929小鼠成纤维细胞（L929）的细胞毒性及其可能导致细胞周期停滞、DNA损伤、活性氧（ROS）水平、线粒体膜电位变化和细胞凋亡的触发机制。将细胞体外培养并用不同浓度的黄连素处理24小时。结果表明，当黄连素浓度高于0.05mg/mL时，细胞活力呈明显的剂量依赖性下降；浓度高于0.1mg/mL的黄连素改变了L929细胞的形态。在G2/M期的细胞中，0.1mg/mL组的ROS水平和细胞凋亡率明显升高。黄连素浓度高于0.025mg/mL的组中，每个DNA损伤指标评分（DIS）均升高。当黄连素浓度高于0.005mg/mL时，线粒体膜电位的抵消平衡机制发生明显改变。总之，本研究表明高剂量的黄连素对L929细胞具有细胞毒性，这与导致的细胞周期停滞、DNA损伤、细胞内ROS积累、线粒体膜电位降低和细胞凋亡有关。
