Yang Weifeng, Ma Lina, Li Sidi, Cui Kaiyu, Lei Lei, Ye Zuguang
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Molecules. 2017 Jun 9;22(6):943. doi: 10.3390/molecules22060943.
Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of () and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure-activity modeling indicated that evodiamine may cause cardiotoxicity. However, previous investigations have indicated that evodiamine has beneficial effects in patients with cardiovascular diseases and there are no previous in vitro or in vivo reports of evodiamine-induced cardiotoxicity. The present study investigated the effects of evodiamine on primary cultured neonatal rat cardiomyocytes in vitro, and on zebrafish in vivo. Cell viability was reduced in vitro, where evodiamine had a 24 h 50% inhibitory concentration of 28.44 µg/mL. Cells exposed to evodiamine also showed increased lactate dehydrogenase release and maleic dialdehyde levels, and reduced superoxide dismutase activity. In vivo, evodiamine had a 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations. This study indicated that evodiamine could cause cardiovascular side effects involving oxidative stress. These findings suggest that cardiac function should be monitored in patients receiving preparations containing evodiamine.
吴茱萸碱是一种生物活性生物碱，被指定为（）质量评估以及含有该植物的中药的生物标志物。我们之前报道过，定量构效关系模型表明吴茱萸碱可能会导致心脏毒性。然而，先前的研究表明吴茱萸碱对心血管疾病患者有有益作用，并且之前没有关于吴茱萸碱诱导心脏毒性的体外或体内报道。本研究调查了吴茱萸碱对原代培养的新生大鼠心肌细胞的体外作用以及对斑马鱼的体内作用。体外实验中细胞活力降低，吴茱萸碱的体外24小时50%抑制浓度为28.44μg/mL。暴露于吴茱萸碱的细胞还表现出乳酸脱氢酶释放增加、丙二醛水平升高以及超氧化物歧化酶活性降低。在体内，吴茱萸碱的10%致死浓度为354 ng/mL，并诱导心脏功能障碍，心率和循环变化以及心包畸形证明了这一点。本研究表明吴茱萸碱可导致涉及氧化应激的心血管副作用。这些发现表明，接受含吴茱萸碱制剂的患者应监测心脏功能。
