Matrine is major active component in Sophora flavescens Ait that plays pharmacological activities against inflammation, tumors and virus. However, potential toxicity of matrine and its possible toxic mechanisms have not been carefully studied. The aim of the study is to assess the toxicity of matrine on mouse liver cells and to investigate the potential ROS-associated mechanisms. Mice were randomly divided into three groups: vehicle control (normal saline), low-dose (50 mg/kg), and high dose (100 mg/kg) groups. Mice in each group were intraperitoneally injected with matrine daily for 7 d. The livers were collected for analysis of histopathological changes and HO-1 protein expression. Serum was collected for analysis of aspartate aminotransferase and alanine aminotransferase activities. Mouse liver NCTC cells were treated with matrine for certain time, and cell viability, cytotoxicity, apoptosis, expression of proteins, activities of caspase-3 and caspase-9, and levels of ROS generation, mitochondrial membrane potential, and ATP were examined. Increased activities of AST and ALT in serum, and vacuolar degeneration of cytoplasm in liver tissues were observed after treatment. Suppression of cell viability, increase of cytotoxicity, induction of apoptosis, alteration in the expression of apoptotic-related proteins, and activation of caspase-3 and caspase-9 were shown in matrine-treated NCTC cells. Furthermore, matrine induced ROS generation, and suppressed mitochondrial membrane potential and ATP levels, however, the antioxidant N-acetylcysteine reversed matrine-induced hepatotoxicity and ROS generation. These findings suggested that matrine stimulated the generation of ROS, which was possibly involved in matrine-induced toxicity in mouse liver cells in vitro and in vivo.

苦参碱为主要活性成分苦参具有抗发炎，肿瘤和病毒药理作用的Ait。但是，苦参碱的潜在毒性及其可能的毒性机理尚未得到仔细研究。这项研究的目的是评估苦参碱对小鼠肝细胞的毒性，并研究与ROS相关的潜在机制。将小鼠随机分为三组：溶媒对照（生理盐水），低剂量（50 mg / kg）和高剂量（100 mg / kg）组。每天腹腔注射苦参碱7天。收集肝脏用于分析组织病理学变化和HO-1蛋白表达。收集血清用于分析天冬氨酸转氨酶和丙氨酸转氨酶的活性。用苦参碱处理小鼠肝脏NCTC细胞一定时间，并观察其细胞活力，细胞毒性，凋亡，检查蛋白质的表达，caspase-3和caspase-9的活性以及ROS的产生水平，线粒体膜电位和ATP。治疗后观察到血清AST和ALT活性升高，肝组织液泡空泡变性。在苦参碱处理的NCTC细胞中显示出细胞活力的抑制，细胞毒性的增加，凋亡的诱导，凋亡相关蛋白表达的改变以及caspase-3和caspase-9的激活。此外，苦参碱还诱导了ROS的产生，并抑制了线粒体膜电位和ATP水平，但是，抗氧化剂 治疗后观察到肝组织中空泡和胞浆的空泡变性。在苦参碱处理的NCTC细胞中显示出细胞活力的抑制，细胞毒性的增加，凋亡的诱导，凋亡相关蛋白表达的改变以及caspase-3和caspase-9的激活。此外，苦参碱诱导ROS生成，并抑制线粒体膜电位和ATP水平，但是，抗氧化剂 治疗后观察到肝组织中空泡和胞浆的空泡变性。在苦参碱处理的NCTC细胞中显示出细胞活力的抑制，细胞毒性的增加，凋亡的诱导，凋亡相关蛋白表达的改变以及caspase-3和caspase-9的激活。此外，苦参碱还诱导了ROS的产生，并抑制了线粒体膜电位和ATP水平，但是，抗氧化剂N-乙酰半胱氨酸逆转苦参碱诱导的肝毒性和ROS的产生。这些发现表明苦参碱刺激了ROS的产生，这可能与苦参碱在体外和体内对小鼠肝细胞的毒性有关。